Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

 
   
  Vancomycin
(Clinical Application and Pharmacokinetics of Vancomycin)

..   
    
5 6
Vancomycin  !"# $%! &#''(#)*+& ,%-$ ./01# methicillin-resistant
Staphylococcus aureus (MRSA) ?@ methicillin-resistant, coagulase-negative Staphylococcus species ?@ .0
# FGHI!J(-%$& Pharmacokinetics ?@ Pharmacodynamics %F"0N&!F!I@(JO(JO&0 ?@!F!?-#-"#(
00# *+&,?-"@F , ! therapeutic index %?FJI!'Q #$0#'N& F##'& '.0%&#''(#) !"
 -! R! $&" $((/ 1.0& #$'I%ST1#''(#) -&0!#'00#?JJ'.0?* # #(J#'&&
!I!-"0*+&,?-"@' OF!'+&?@F! N& ##(J#''G#-U&@(##'%$& pharmacokinetic ?@
pharmacodynamic N0 Vancomycin (/ (J"!F!IF(VI'(JJGF@#'%#'?1%U%!I" #N&0#(J#'&
$(#@"/*+&, 
789:; <9:5





/ 
 (Mechanism of Action / Pharmacology)
Vancomycin 00#W%SX Y $#'( J (/  #'I(  F'U cell wall ##'( J % D-Ala-D-Ala ?@( J (/ 
transglycosylase (J(/#'@$@"0 building block unit 00## lipid carrier %& peptidoglycan !"I!'QI'&-"0
$& peptidogycan 0"0?0@?@ #$ cell lysis ?@-@ !W%SX  bactericidal1 .0#-?"#'00#W%SX
N0?-#-"#(J#@G"! beta-lactam antibiotics $((/ !" #$#'$./0N&!#@G"! (cross resistance) #('"
%(/I0 0##/ Vancomycin 0!*@-"0 permeability N0 cell membranes ?@(J(/#'J#' RNA synthesis 
vancomycin !*@  bactericidal -"0 ./0#@G"! gram-positive I"V" 0" '#^-!I'(J ./0 streptococcus
faecalis ! FG H I!J( -   ?F" bacteriostatic I  '( J ./ 0 Gram-negative (/  1J"  $./ 0 -" 0  vancomycin 0( 
.0!##'@$ permeability N0 outer membrane2
Vancomycin Spectra
Vancomycin !'I%ST1#'a" ./0#@G"! gram-positive I"V" Y$1J" ./0 Staphylococcus
aureus ('!%(/ methicillin-resistant strains) ?@ Streptococcus species I"V" sensitive -"0 vancomycin Y$
S''!-N0-( vancomycin 0(/!'I%ST1-"0#'a" ./0#@G"! gram-negative $& 1 @^#&0 ?-"0" '#^
-!&*@  synergistic activity !.0&'"!#(J#@G"! aminoglycosides 0##/(1J"T%&0 I##'
-$ ./0?JF% ' (Bacterial diarrhea) %!I -G!##'-$ ./0 Clostridium difficile '.0 staphylococcal enterocolitis
(/I!'Q&#''(#)$& vancomycin '+?JJ#''(J'% $&0"!'I%ST1 I'(J vancomycin '+?JJN0
c$ N&@0$ @.0$$(/ !'YU#'&'(#)T#'-$ ./0 methicillin-resistant Staphylococcus aureus '.0
multi-resistant strains N0 staphylococci 0.d, '(#)T#'-$ ./0 staphylococcal '.0 streptococcal *+&,%?1&
#@G"! beta-lactam antibiotics ?@'(#)T endocarditis %!I -G!# ./0#@G"! streptococci,



























































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1

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

staphylococci ?@ enterococci O  *+& ,  ?1&  #@G" ! penicillin . 0 #e  G J(  1J"  ' ! ! 0G J( - # 'HU N 0
vancomycin-resistant enterococci (VRE) ?@!J strains N0 ./0 Staphylococcus aureus %!#'$./0-"0
vancomycin (intermediate vancomycin resistance)3 $((/F'1'HQF! !I!N0#'&#"0#' @.0#&
%G#F'(/ 1.0R0#(eV '.0#'?1'"#'N0#'$./0
,-./01Vancomycin !.0&%@0$ @.0$$ !(#&#''(#)T#'HU-$ ./0?#'!J#%'G?' Y$ c10" #(J
./0 methicillin-resistant Staphylococci ?@&*+&,%  immunocompromised host ?@ .0#!YF'I'&0+"
#@G"! glycopeptide O?-#-"##@G"!0. d  !" #$#'?1&N&!#@G"! (cross-reaction) #(J 
0.d ?@%&I!'Q&#''(#)T#'-$ ./0?#'!J#*+&,%?1&#@G"! penicillin ?@/'.0 cephalosporin $& I'(JN&0J"&Y$%( N0 Vancomycin (/$(?I$'@ 0$-'% 1
2034 1 12
34521
4  vancomycin2
1. Admission to intensive care unit - Selective
15. Febrile neutropenia
decontamination of the digestive tract
16. Infection due to corynebacterium
2. Anaerobic streptococcal infection
17. Infection due to Staphylococcus aureus
3. Anthrax
18. Infection due to Staphylococcus epidermidis
4. Antibiotic induced pseudomembranous
19. Infection of intravenous catheter
enterocolitis
20. Meningitis
5. Bacterial endocarditis; Prophylaxis
21. Methicillin resistant Staphylococcus aureus
6. Bacterial infection due to Bacillus
infection
7. Bacterial infection of eye
22. Operation on musculoskeletal system 8. Capnocytophaga canimorsus infection
Postoperative infection; Prophylaxis
9. Cardiovascular surgical procedure 23. Operation on nervous system - Postoperative
Postoperative infection; Prophylaxis
infection; Prophylaxis
10. Cardiovascular surgical procedure 24. Pneumococcal infectious disease
Postoperative infection; Prophylaxis
25. Pneumonia
11. Clostridium difficile infection
26. Postoperative infection; Prophylaxis - Surgical
12. Clostridium difficile infection; Prophylaxis procedure on thorax
Hemopoietic stem cell transplant; Prophylaxis
27. Streptococcus bovis infection
13. Endocarditis
28. Streptococcus group B infection
14. Endocarditis - Infection due to enterococcus
29. Streptococcus pyogenes infection
30. Streptococcus viridans group infection

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2

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

.0#1JeV ##(J#'$./0 vancomycin N0 ./0 1!!#N/ $((/% Center for Disease Control 
$&00# !-'#''.0YJ 1.0? #HwU#' @.0#& vancomycin 0" !I! '!%(/T% !"?&
@.0#& vancomycin $(?I$'@ 0$-'% 2 (MMWR 44:No RR-12, September 22, 1994)
2034 2 89:
9;<93
:
52  vancomycin =99;<>3=952:
52 
vancomycin 5
=
>?@:
<9 ?7
7A@ vancomycin ;CA
#''(#)T#'-$ ./0%'G?' 0(!I -G!# ./0#@G!" beta-lactamzresistant grampositive
#''(#)T#'-$ ./0 0(!I -G!# ./0#@G"! gram-positive microorganisms *+&,*+&O ?1&
#@G"! beta-lactam antimicrobials ?JJ'G?'
T Antibiotic-associated colitis % !"-0JI0-"0#''(#)$& metronidazole '.0 T
Antibiotic-associated colitis %'G?'?@ 0(-'Q?#" -
& Prophylaxis I'(JT endocarditis *+&,%!F ! I I+-"0#' #$T endocarditis $(#@"
-!F?N0 the American Heart Association
& Prophylaxis I'(J major surgical procedures % #N&0#(J#' @ Q"1# prosthetic materials
'.0 devices -"d ( " cardiac ?@ vascular procedures ?@ total hip replacement -&)
= >?@:
<9;7A?7
7 ?@;7A
6?@ vancomycin ;CA
&  Routine surgical prophylaxis
&  Empiric antimicrobial therapy I'(J*+&,%!T febrile neutropenic
'(#)T#'-$ ./0%*@#'% blood culture 1J" J#-"0 ./0 coagulase-negative staphylococci
1 1 F'(/
&  Continued empiric *+&,%*@ culture N0 ./0#@G!" beta-lactamzresistant gram-positive
microorganisms @J
&'+?JJN0 Systemic '.0 local 1.0  prophylaxis I'(J#'-$ ./0'.0#' colonized N0 ./0
*+&,% I" indwelling central '.0 peripheral intravascular catheters
T Selective decontamination of the digestive tract.
1.0#'#($ (Eradication) MRSA colonization
&  Primary treatment T antibiotic-associated colitis
&  Routine prophylaxis I'(J%'#?'# #$%! /(#-(-#" #HwU!# (very low-birthweight
infants)
&  Routine prophylaxis *+&,%-&0 N&'(J#'% peritoneal dialysis '.0 hemodialysis "
ambulatory 0"-"0 .0
'(#)(chosen for dosing convenience) #'-$ ./0%! I -G!# ./0#@G"! beta-lactamzsensitive
gram-positive microorganisms *+&, renal failure
& vancomycin solution  topical application '.0 irrigation



























































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3

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)


7/890:;0<=>

1-
0#' !"1 'IFU##'&%1 J $&J"0N0 Vancomycin $&?#" 0#'1)-"0 -O !(#1J $& 1! !#
N/*+&, %!e ( I-"0#' #$1)-"0 - *+&,%!T#'%N0 -%J#1'"00+"#0" ?@& '.0*+&,% $&'(J
#@G"!0.d %!1)-"0 -'"!$& ?@ T red-man syndrome O !(# #$##''(J0(-'#'&% !" !I!
0##/(I!'Q1J0#' !"1'IFU0.d O 01J $& !"J"0!#(# " 1)-"0+, *@-"0'JJ @.0$, *@-"0
'JJ@0$ @.0$( ?@0.d $(?I$'@ 0$$(-"0 /
1. *@-"0 - (Renal Effects) Q?!&"#'}#)I(-U%$@0 !"1J" vancomycin I -GN0#' #$
nephrotoxicity ?-"!# '}#)F%1!F!I(!1(SU'"'$(J vancomycin #'?I @.0$#(J
F! 1)-"0 -N0 Y$#'}#)I"V" #'}#)?JJ retrospective O*@#'}#) @"/1J"!'
F! 1)-"0 -%I(!1(SU#(J#' $&'(J vancomycin 0"($  &0#"'.0 %"#(J'&0@ 5 ?@!#'}#)
/%  #'}#)N$V"N0 Pestotnik ?@FH % $&'0GJ-( #'HUN0#' #$1)-"0 -N0*+& ,
 1750 F "!F" %"#(J'&0@ 1.4 0##/ (1J"0GJ(-#'HU$( #@" 1!N/*+&,% $&'(J vancomycin
'"!#(J#@G"! aminoglycoside OI0$F@&0#(J*@#'}#)0.d Y$I"!#%(/I"%  #'}#)F?@I(-U %
1J"0GJ(-# 'HU$( #@"(/ 1!!#N/ 3-4 %" #'}#)%!#'& vancomycin '"!#(J#@G!"
aminoglycoside !.0 %J#(J#' $&'(J 1 vancomycin $d
2. Hematologic Effects 0#'N& F#@G"!/%I!'Q1J $& " Agranulocytosis, Drug-induced
eosinophilia, Immune thrombocytopenia, Neutropenia ?@ Thrombocytopenia O0#'N& F#@G"!/ ' T%%
I!'Q1J $&J"0F.0 Neutopenia O( !"%'JI -G%($ N0#'%& #$ T neutopenia N0 ?-"!J
I!!G-% .0" vancomycin 0!1)Y$-'-"0#'I'& granulocyte '.00!*@ IY$*"%'JJT+!F!G& #(
T neutropenia % #$N//!#( #$N/T 2-6 I($U@(#'& ?@I!'Q#@(JI+"#- $&T 1-16 (@(G$
& $((/# -&0&#" 2 I($U#^F'%#'-$-! CBC 'd
3. *@-"0+ (Otic Effects) ##'}#)1J"0GJ(-#'HUN0#' #$ ototoxicity N0F"0N&- ?@( !"!
N&0I'G%$(  ##(JF!I(!1(SU$(#@" ! 1#'}#)%1J"F! 1)-"0+N0 #$N/ !.0&'"!#(J
0.d %!F! 1)-"0+0+$" & ?@1)-"0+N0@$@ !.0@$N$#'&@ 0##/(!F!F$ ^N0
*+& VJ%"%!F !F$" vancomycin !" $&!1)-"0+' I'(J'$(J%!'"% & #$1)-"0+(/
1J"0+" " 80-100 mg/L NH%J#'}#)'"F! 1)N0-"0+ #$N/ !.0'$(J% peak 
25-50 mg/L ?@ trough  13-32 mg/L Y$ !"!# ''JG$( "'$(J% peak '.0 trough % '$(J/ ($F!
1)-"0+N0
4. *@-"0'JJ(?@@0$ @.0$ (Cardiovascular Effects)
Cardiac arrest !'#' #$T Cardiac arrest *+& , 2 '% $&'(J IV vancomycin ?@F$"
 # N&0#(J#'J''&?#"*+&,0(-'%  '^ # 
Hypotension !'#' #$T Hypotension ##' $&'(J vancomycin O .0""!F!I(!1(SU
#(J#'J''0(-'%  '^ #  (infusion over less than 30 minutes) ?@ # .0#(J#'@(N0I' histamine O
#'% '#" anaphylactoid reaction.

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  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

Thrombophlebitis !'#' #$T$(#@"/ '&0@ 13 N0*+&,%(/ !$% $&'(J% peripheral

venous catheters
5. red-man syndrome !'#' #$T$(#@"/N/ '&0@ 5-47 Y$ ./0" #'%!F ! #N&0
#(JI' histamine Y$0#'?I$N0T$(#@"/ $&?#" '&0+JJ, F(, I(, ^J&0#, @J#, !*.?JJ
maculopapular rash J' H &0# & F0 @(?@?N ?@0!T hypotension OT red- man syndrome /
!(# #$N/ !.0J'' vancomycin % IV '^ #  '.0&F! N&!N&N0%!# #  Y$0#'!(# '! #$
@(##'&'!H 15-45 % ?@0#' T@(##'G$'!H 10-60 % $((/#'R0#(
T$(#@"/I!'Q% $&$&#' & vancomycin 0(-' '^ !" # 15 mg/min I'(J#'& antihistamine '.0
corticosteroid #^1J"I!'Q"@$F!'G?'?@Y0#IN0#' #$T$(#@"/ $&
Drug interaction
Y$I"!#eV '.0 Drug interaction N0 vancomycin !(# #N&0#(JFGHI!J(-%$&
pharmacodynamic !##"FGHI!J(-%$& pharmacokinetic N0
1. aminoglycoside antibiotic: #'& vancomycin '"!#(J#@G"!#@G"! aminoglycoside !
*@ 1! nephrotoxicity N0 (%&0GJ(-#'HUN0#' #$1)-"0 - 1! I+N/) OY$#-?@&#'&#@G"!
aminoglycoside 1 $d (/ #^I!'Q I -G& #$ nephrotoxicity $&?@& $((/ !.0!#'& vancomycin '"!
$&#(#(J#@G"! aminoglycoside #^F'-&0!#'-$-!'$(JF! N&!N&N0 serum creatinin '
%G#d ( ?@0##/#I!'Q% $&F'%!#'-$-!($'$(JN0%(/ I0 1! -!0#$&
2. warfarin: !.0!#'& vancomycin *+&,% $&'(J#''(#)$& warfarin 0+"$&(/ 1J"0!*@
-"0#' 1! hypoprothrombicnemia effect N0 anticoagulant $& Y$#@ #N0#' #$*@$(#@"(/( !" %%'J
?"($ ?-"!*@#'}#)1J"*+&,%!#'& vancomycin '"!#(J warfarin (/!F" prothrombin time 1!!#
N/ '&0@ 45 !.0 %J#(J*+&,% $&'(J warfarin 1 $d $((/*+&,% $&'(J#''(#)$& warfain %
 -&0!#'& vancomycin '"!$&(/ F'!#'-$-!'$(JN0 prothrombin time ratio (INR) %  baseline
#"0#' '!& vancomycin ?@&@(#(/#^F'-&0-$-!'$(JN0 INR '%G#(#"F" INR 0+""
R!?@F%
3. heparin: #'&*+&, $&'(J heparin ?@ vancomycin '"!% IV line $#( %& #$ inactivation N0
vancomycin
4. metformin: Y$#-?@&#'& metformin '"!#(J%! F H
G I!J(-  cationic drugs Y$*@N0#' #$
drug interaction '"%(/I0F.0I"*@&'$(J metformin 1!I+N/ %(//%(/(/ .0# vancomycin #^ 
%FGHI!J(-  cationic drugs $((/#'& vancomycin *+&,% $&'(J metformin '"!$&(/-&0F0
'!($'(#'-$-!?@'(JN$ metformin ?@/'.0 vancomycin
5. Indomethacin: #'& vancomycin  $^#% $&'(J indomethacin '"!$&(/-&0&F!'!($'( 
1 }) .0#!*@%&F" Vd $^# 1!I+N/ ?@ elimination half life N/!# O0 #$##'%
indomethacin !*@%& glomerular filtration rate (GFR) @$@

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5

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

D7  D@E F (Basic clinical Pharmacokinetics parameter)

 Vancomycin Y$I"!#Q+##($00#'+?JJ% !"!# ' @?@%eII0"I!J+'HU Y$#'
J#'#'0N0 glomerular filtration (!##"'.0 %"#(J'&0@ 90; -'% 3) $(#@"J/ ''Y$#'c$?JJ intermittent intravenous infusion (1 (Y! 0"&0) ?@F'@# @#'c$ N&%@0$ @.0$$ .0 #!'"
I!'Q%& #$T tissue necrosis H -?"%c$ $& ! oral bioavailability - (&0#"'&0@ 10) $((/#'
-$ ./0% systemic  !"I!'QJ''$&#''(J'% $& ! plasma protein binding '!H'&0@ 55 ?@
N$%?*+&,%!&%#'%#-F.0 30 mg/kg/day Y$I!'Q?J"& $& 2-4 F'(/-"0( ?@*+&V"%!
/(#-(#-?@!&%#'%N0 -%$ I!'Q& $&N$Q 1000 mg %G#d 12 (Y! (2 g/day) 0##/
(1J"Y'F'.0ITJ0"I!'Q!*@%&F" Pharmacokinetics parameter @?@00#  $& $('@ 0$
-'% 3

ABAC97 (Absorption)
$+$O!%'JJ% $0' $&&0 $((/#'H& 1.0#''(#)#'-$ ./0% ?JJ systemic infection (/
-&0J''%@0$ @.0$$ Y$-(%@@% !&F0. D5W '.0 NSS '!H 100-250 ml Y$#'J''
&?#"*+&,(/F'&0"&d T' @0"&0 60 % (0(-' !" # 150 mg /%) 1'#*+&,  $&'(J
0(-'%  '^ # 0%& #$T red-man syndrome ?#"*+&, $& ?@ !"F'J''%#'c$ N&#@&! ./0
.0#%&*+&,!0#'$ J! ?$ J' H%c$ $& I'(J#'HN0#'& 1.0'(#)T enterocolitis (/
I!'Q&*+&, $&'(J%#''(J'% $& Y$1J"I!'QQ+#$+$O! $&&0!# ?-"0" '#^-!T%!# '
0(# IJN0@ I&!#d '.0*+&,!T#'HU% N0 -J#1'"0 01J'$(J @.0$ 1! I+N/ $& (0I+Q 1.2- 3.4
mg/L) Y$ c10" !.0!#'&N$I+d ' @


;>2 (Distribution)
Vancomycin I!'Q#'-( N&  ./0 .0'"#?@N0 @'"# " #@&! ./0@, @/(,
#'$+#, ascitic fluid, peritoneal fluid, pleural fluid ?@ synovial fluid ?-"I!'Q?1'"*" BBB N&I+" serebrospinal
fluid (CSF) $&&0!# # !"!#'0(# IJN0 ./0G&!I!0 %#@(J#(#!#'0(# IJN0 ./0G&!I!0#^I!'Q N&
 $&!'$(JQ therapeutic concentration I'(J#'(J#(JY'- @.0$ (protein binding ) N0(/ 1J"
vancomycin !(#(J#(J albumin @(# Y$!F" protein binding c@'!H'&0@ 30-60
! distribution phase %10I!F'  !% 0SJ#' @?@N0'$(J @.0$$&
multicompartment model " two '.0 three compartment model Y$@(##'&%@0$ @.0$$?@&
distribution phase I'(J"?'#! half-life '!H 7 % -!$& distribution phase "% 2 O! half life
'!H 30-90 % #'H%& two compartment model 0SJ(/1J"!F" Vd '!H 0.580.22 L/kg
Y$!F" Vd N0 central compartment '!H 0.220.12 L/kg
72.
C97 (Metabolism)
Q?!&"N&0!+@##'(I"V"1J" Vancomycin Q+#N(J00#% - @(# ?-"0" '#^-!!#'}#)
1J" @(##'& IV infusion ?@&I!'Q1J/$?@0G' $& ?I$"!#'#($Y$ nonrenal
clearance $& 0##/ (1J" nonrenal clearance % #$N/ 0!Q'!H'&0@ 5-20 N0 total clearance 



























































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  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

'"# ?-"eGJ(#^( !*@#'}#)%?-#-"#(0+"!#' $^$(#@"/ ?@#''(JN$#'HN0*+&,%!

#'%N0-(J*$#-#^0( !"!F! -&0%

834 1 ?I$ 2-compartment pharmacokinetic model !.0 C ?%'$(JF! N&!N&, a ?@ b ?% elimination
constants, e ?% N0 natural logarithm, t ?% @, A ?@ B ?% zero time intercepts N0 a ?@ b -!@$(J,
Ko ?% infusion rate constant, Vc ?% volume of the central compartment, Vp ?% volume of the peripheral
compartment, K12 ?@ K21 ?% intracompartmental rate constants, ?@ KEL ?% elimination rate constant #
central compartment


E>A (Elimination)
Q+#N(J00#'+% !"!#' @ ?@ Y$ glomerular filtration @(# (0! renal tubular secretion '"!
$&) $((/##'%N0 -*+&,@$@ #'#($#^@$@-! $& Q+#N(J00#'!H'&0@ 80-100
N0'!H%  N& '"#*+&,%! #'%N0 -#- Y$! elimination half life N0'!H 2.9-13.3
( Y! 0" '#^-!F"$(#@"/0!F!?-#-"#( $&F"0N&!#?-"@#'}#) I" elimination half-life N0
*+&,%!# '%N0 -J#1'"0(/ 0!F"Q 7 (
#'HN0*+&,%! #'%N0 -J#1'"0'.0*+&, -'IG$%&% $&'(J#'% dialysis (/ 1J"
*@#'%JN0#'% dialysis -"0#'#($N/0+"#(J $N0#'% dialysis (/d Y$1J"#'% hemodialysis !*@
-"0#'#($&0!# O &0#"'&0@ 10 N0N$% $&'(J %"(/%!#'Q+##($*"% hemodialysis $((/
@(#'% hemodialysis  !" -&0& 1! ?#"*+&,0# I"#'% peritoneal dialysis (/( !"!N0& I'G%($ 
Y$!'%(/ %#@""  !" $&Q+##($% peritoneal dialysis ?@%'"Q+##($'!H%-"d #( O0
%&-&0&*+&,  $&'(J 1!T@(##'% peritoneal dialysis
#'HN0*+&I+0G1J" !#' @?@% Pharmacokinetic N0 #$N/ Y$1J"F" Vd  1! !#N/
#"*+&V" Y$F" Vd N0*+&I+ 0G-"0N0*+& V"!F" '!H 0.76 L/kg -"0 0.46L/kg OF$" *@##'% !#'



























































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7

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

(J#(J .0/ .0N0'"# 1!!#N/ 0##/( 1J" elimination half-life N0*+&I+0G#!^ F"N/$&
.0#! clearance N0@$@ $((/ !.0!#'&?#"*+&I+ 0GF'1'HQ#' @ ?@$(#@"N&-&/$& 
1.0R0#( !"&!#'II!N0 #$N/
2034 3 ?@=99;<;A3
B;< =B4@34 Pharmacokinetics 1
4  vancomycin
Disease state/condition Half-life (hr)
Volume of distribution (L/Kg)
?7?Q
*+&V", !#'%&%N0 - 8 (7-9)
0.7 (0.5-1.0)
N$#-F.0 30 mg/kg/day ?J"
#-
& $& 2F'(/-"0(
*+&V", renal failure
130 (120-140) 0.7 (0.5-1.0)
T underhydration '.0
overhydration !" $&!*@-"0 volume
of distribution N0
Burn
4
0.7
.0#! half-life %I(/@
$((/*+&,J'0-&0
J''&%G#d 6-8 hr 1.0F
therapeutic trough concentration
&
Obesity (> 30% over BMI) 3-4
Vd = 0.7 IBW
N$-"0(-&0F$-! TBW, F$
, !#'%&%N 0 - 
Vd # IBW ?@ .0#!
#-
half-life %I(/@ $((/*+&,J
'0-&0J''&%G#d 8 hr
1.0F therapeutic trough
concentration &
55R 
F'(/?'#N0#'&(/ -&0!#' @.0#N$ (Dose) ?@ interval N0#'& (dose interval) &
!I!?#"*+&,?-"@' Y$-&0FQ 0G, /(# ?@ renal function N0*+&, OS#' @.0# dosage
regimen $(#@"!/ 0+"@'+?JJ Y$?-"@S(/-"#^!N0& #($%?-#-"#(00#  $((/#'-($I" @.0#
S#'$(/#^-&0N/0+"#(JF! !I! F!I$# ?@'IJ#'HUN0*+&& ?@F'-&0!#'-$-!-'($'$(J
 @.0$ '0"&0I($U@ 1 F'(/ 1.0'(J @N$#"'$(J0+"'$(J%  !I! I'(J
?%#' @.0# dosage regimen '.0S#'1'H @.0#N$?@ interval N0#'& (dose interval) (/!
'@ 0$?I$$(-"0 /
1. ,-IJ;JE>


E
. (Package insert)
J')(%*+&*@- $&? &" *+&,%!T#'HU%N0 -J#1'"0 (Renal impairment) (/F' $&'(J
 maintenance doses N$ 250 -1000 mg %G#d 3-4 ( ?@Q&*+&,!T anuric ?&&N$ 1000 mg
%G#d 7 -10 (?% I'(J daily dosing (/1'H-!F" Creatinine clearance $(?I$'@ 0$-'% 4



























































..............................................
8

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

2034 4 daily dosing 1
4  vancomycin :<
F@3 Creatinine clearance

Creatinine clearance mL/min
Vancomycin dose mg/24 hours
10
155
20
310
30
465
40
620
50
770
60
925
70
1080
80
1235
90
1390
100
1545
Initial dose N0 vancomycin !"F'&0#" 15 mg/kg ?@ N$%  !I!%IG$?@ interval N0#'&
(/I!'Q% $&#'$(JF! N&!N&N0#'?I @.0$ (serum drug concentrations) I'(J*+&,% - !"!
#'%?@&(/ (anephric patients) !"I!'Q&-'N&J/#' @.0#N$#'& $& 0##/ *+&,% $&'(J
 initial dosage  15 mg/kg N0/(#-((/ !F!-&0#'& maintain stable concentrations N0  1.9
mg/kg/24(Y!
2. 20 M
,JA,0 Brown DL and Mauro LS
F?I'(J#' @.0#N$-!S$( #@"/F.0&*+&, $&'(J Loading dose %"#(J 15 mg/kg ?@
I'(J maintenance dose (/&1'H @.0# dose ?@ dosing interval -!'@ 0$-'% 5
2034 5 dose =9 dosing interval 1
4  vancomycin G;:
1H 1
4 Brown DL and Mauro LS
E6?  40-55 kg
E6?  55-75 kg
E6?  75-100 kg
Creatinine clearance mL/min
Dose= 500 mg
Dose= 750 mg
Dose= 1000 mg
81-100
q 8 hr
q 12 hr
q 18 hr
54-80
q 12 hr
q 18 hr
q 24 hr
40-53
q 18 hr
q 24 hr
q 36 hr
27-39
q 24 hr
q 36 hr
q 48 hr
2034 5 dose =9 dosing interval 1
4  vancomycin G;:
1H 1
4 Brown DL and Mauro LS ( 3
)
E6?  40-55 kg
E6?  55-75 kg
E6?  75-100 kg
Creatinine clearance mL/min
Dose= 500 mg
Dose= 750 mg
Dose= 1000 mg
21-26
q 36 hr
q 48 hr
q 72 hr
16-20
q 48 hr
q 60 hr
q 84 hr
13-15
q 60 hr
q 84 hr
q 108 hr
10-12
q 72 hr
q 108 hr
q 144 hr



























































..............................................
9

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

3.
1- Nomogram ,0 Moellering I;<T;

.0!#"! Patient-specific factors 1 2 factor %!#' @?@ !.0& pharmacokinetics dosing
method O $&?#" /(#-( ?@ Creatinine clearance N0*+& , $((/I!'Q 0 nomogram 1./!'G#-U
&I'(J#' @.0#N$ ?@ dosing interval  uncomplicated patient $& O Moellering dosing nomogram 
nomogram ?'#%!#'!'G#-U&#'FHN$ vancomycin I'(J*+&,%!T#'%&%N0 J#1'"0#(0"?1'"@ (-'% 7 '.0 T1% 2) O R!N0 nomogram $(#@"/F0. %&'$(JF! N&!N&N0
 c@% steady- state  15 mcg/ml ('.0 15 mg/L) Y$#'& nomogram $(#@"/(/-&0!#'FH
I($I"N0 Creatinine clearance -"0/(#-(N0*+&, (Creatinine clearance//(#-( ) 1.0& creatinin clearance
00#!"N0 mL/min/ kg O F"$(#@"% $&/I!'Q#@(J 1'H @.0# maintenance dose '+N0
mg/kg/24 hr N0 vancomycin $& Q&*+&,!T#'%&%N 0 -%J#1'"0 ?&& loading dose  15 mg/kg
?-"0" '#^-! nomogram $(#@"/ !" $&# $ dosing interval N0#'& &&
 Pharmacokinetic dosing method (/F!I(!1(SU'" vancomycin clearance #(J creatinin clearance
0#0"% !&I'& Moellering nomogram $((/N$? (dosing recommendation) #%(/ I0S 
!F"% #@& F#( ?-" trough concentration 0!F" %?-#-"#(%(//%(/ (/#^ .0!#'$(JF! N&!N&N0%(/
peak ?@ trough concentration (/ !"I!'Q& $&0" 1 -"0 nomogram $(#@"/ I'(J#'FH
N$ maintenance dose 1.0& $&'$(J% steady- state  15 mg/L I!'QFH $&#I+-'$(?I$
-'% 6
2034 6 =H4 @ maintenance dose 1
4  vancomycin
FH Maintenance dose #I+-' MD = Css . Cl
!.0 MD = maintenance dose


.I+-'% 1
Cl (mg/hr/kg) = 0.695 (CrCl in ml/min/kg) + 0.05
Css = 15 mg/L
?%F" Cl ?@ Css $(#@"N&-&@I+-'% 1  $& 
MD (mg/hr/kg) = [(15 mg/L) . 60 min/hr)/1000 mL/L][ 0.695 (CrCl in ml/min/kg) + 0.05]
MD (mg/hr/kg) = 0.625(CrCl in ml/min/kg) + 0.05


.I+-'% 2
#'&S# '$(#@"(/ !" $&!F !G"#I@(JO(JO&0 Y$F" creatinin clearance N0*+&,(/I!'QFH
$&# 2 I+-'@(#d $&?#"
1. Cockcroft-Gault method &I'(J*+&,%!/ (#-(#-
CrCl = [(140-0G). BW]/ (72.Scr)

 1}
CrCl = { [(140-0G). BW]/ (72.Scr)}. 0.85

 1}V
2. Salazar-Corcoran method &I'(J*+&,%!T obesity
CrCl = {(146-0G) [(0.287. BW) + (9.74. Ht2]}/(60.Scr)


.. 1}V
CrCl = {(137-0G) [(0.287. BW) + (12.1. Ht2]}/(51.Scr)

 1}
I'(JF?#' @.0# Dosing interval (" hr) % !I!(/ I!'Q% $&$&#'?J" dosage
rate   clinical acceptable dose " 1000 mg



























































..............................................
10

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

2034 7 Moellering Nomogram Vancomycin dosing chart

1. FH CrCl N0*+&,$&S Cockcroft-Gault method '.0 Salazar-Corcoran method
2. I($I"N0 CrCl -"0/(#-(N0*+&,
3. FH 24 (Y! Maintenance dose -! CrCl % $&#N&0 2
4. *+&,%!F !J#1'"0#'%&%N0 - F' '! & loading dose % 15 mg/kg
Creatinine clearance (mL/min/ kg)
Vancomycin dose (mg/kg/24 hr)
2.0
30.9
1.9
29.3
1.8
27.8
1.7
26.3
1.6
24.7
1.5
23.2
1.4
21.6
1.3
20.1
1.2
18.5
1.1
17
1.0
15.4
0.9
13.9
0.8
12.4
0.7
10.8
0.6
9.3
0.5
7.7
0.4
6.2
0.3
4.6
0.2
3.1
0.1
1.5
** N$*+&,% - !"!# '%?@& (functionally anephric patients) F.0 1.9 mg/kg/hr
$($?@# Moellering RC, Jr, Krogstad DJ, Greenblatt DJ, Vancomycin therapy in patients with impaired renal
function: a nomogram for dosage. Ann Intern Med 1981;94:343-346.

..............................................
11

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

834 2 Nomogram 1
4 Moellering =9@9

4.
1- Nomogram ,0 Matzke

Matzke dosing regimen nomogram % @.0#%! 'I%ST1?@'$ '^#''G#-U@(##'%
pharmacokinetics !&#'FHN$#'& Y$ !"-&0&F!I@(JO(JO&0N0I+-'% pharmacokinetics
(-'% 8 '.0T1% 3) ?-"0" '#^-! nomogram $(#@"/ !" $&!#' %$I0J*+&,%!T obesity (/(#
-(' > 30% N0 ideal body weight) $((/ !"?& 0S$ (#@"/ &#@G"!*+&,' T%$(#@"
0##/*+& N( $&? 1! -!0#" !"F'&S#'$(#@"/#'F$N$#'& ?@ dosing interval *+&,
%-&0% peritoneal dialysis
%!N0 Nomogram $(#@"!/ @(##'%  YF'I'&IF(VF.0 %& peak ?@ though N0'$(J% steady
state  30 mcg/ml ?@ 7.5 mcg/ml -!@$(J Y$ '!-&$&#'&N$N0 loading dose %"#(J 25 mg/kg
?@&-!$& 19 mg/kg Y$ @.0# dosing interval N0#'J''%?-#-"#(00# -!'$(JN0 creatinin clearance
*+&,?-"@' O dosing interval %#$ nomogram $(#@"(/ $&# $N/ 1.0&I0$F@&0#(J"' @%
*+&,O!'$(J creatinin clearance '$(J%?-#-"#(00# I!'Q#($'!H% $&'(JF.0 19 mg/kg 00#
#'"# $& %(//%(/(/ 1.0 & #$#'?%%N0% $&!# '#($00# #'"#T"' @-! dosing
interval $& maintenance dose N$ $! ?@'# peak ?@ trough vancomycin concentration z time
profile ?JJ $!N/0#T@(##'&?-"@ dose ?@ .0# nomogram $(#@"/ &S #' fixed '$(J
peak ?@ trough % steady state @(#Y$ !" $&!#'' ! volume of distribution ?@ elimination rate constant
N0 $((/0!F!?-#-"N0N$%? $& 0##/(!N&0!+@#J#'}#)%? I$& ^" '$(J
 @.0$% $&##'&S$( #@"/ I+#"%F $ 0 &!#  N&0%1'(N0#'&S$( #@"/

..............................................
12

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

Matzke nomogram vancomycin dosing regimen

FH creatinin clearance N0*+&, Y$&S Cockcroft-Gault method
nomogram $(#@"/ !"?&&*+&,%!T obesity
dosing chart $(#@"/! R! 1.0-&0#'& peak ?@ though N0'$(J% steady state  30
mcg/ml ?@ 7.5 mcg/ml -!@$(J
4. & loading dose  25 mg/kg
5. & maintenance dose 19 mg/kg Y$ @.0# dosing interval N0#'J''%?-#-"#(00# -!
'$(JN0 creatinin clearance *+&,?-"@'$('@ 0$$(-"0 /
Creatinine clearance (mL/min)
Dosing interval (day)
!##"'.0 %"#(J 120
0.5
100
0.6
80
0.75
60
1
40
1.5
30
2
20
2.5
10
4
5
6
0
12
$($?@# Matzke GR, Halstenson CE, Olson PL, Collins AJ, Abranham PA. Systemic absorption of oral
vancomycin in patient with renal insufficiency and antibiotic- associated colitis. Am J Kidney Dis. 1987;9:422-425.
2034 8
1.
2.
3.

5. Pharmacokinetics dosing method

R!N0#'FH Initial dosing N0 vancomycin F.0 $&N$%  !I!#(JT#'-$ ./0 -
?" ?@F!'G?'N0#'-$ ./0 O#'FH$(#@"/ (/ -&0!#'FH pharmacokinetics parameter
-"d N0*+&, $&#'& mean parameter %!#'($#@G"!*+&,%!ITN0Y'F'.0#'-$ ./0?@YF'I'&%IQ
-%F @&F@#( '.0% '#0#0""#'FH#F" c@'#'
5.1 <EJT Clerance (estimate of clerance)
 vancomycin Y$I"!#!#'#($0"I!J+'HU'+?JJ% !"!#' @?@00#% - ?@
clearance N0#^!F!I(!1(SU%$#(J creatinin clearance OF!I(!1(SU$(#@"/I!'Q!&#'FH
clearance N0 $& ?@ I+"#'FHN$ (initial dose) $& Y$I+-'%FH-}I-'U% &#'FH
clearance N0 F.0
Cl = 0.625(CrCl) + 0.05
Y$
Cl ?% clearance N0 vancomycin (mL/min/kg)
CrCl ?% creatinin clearance (mL/min/kg)



























































..............................................
13

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

.0#F" creatinin clearance ?-"@F"Q+#%& F"!-'I'(J/(#-(N0*+&, 1'c(/#'

F" creatinin clearance &I+-'N0#'FH(/ F'-&0F"% $&!'$&/(#-(N0*+&, "
#Y@#'(! I#"0 ?@*@N0F" clearance N0% $&(/ #-&0#'&!F" 0+" " mL/min #^I!'Q 0/ (#
-( ( weight factor) N0*+&,!F+H#(JF" clearance N0% $&##'FH$&I+-'%0+"" mL/min/kg $& Y$
weight factor %!&(/&& /(#-(' (total body weight) N0*+&, !""*+&, !T obesity $&'.0 !"
834 3 Matzke dosing regimen nomogram

5.2 <EJT</ volume of distribution (estimate of volume of distribution)

Y$#-?@&F" volume of distribution c@N0 vancomycin !F" %"#(J 0.7 L/kg O#'FH volume
of distribution *+&,%!T obesity (/&& weight factor  Ideal body weight (IBW) ?%
Vd = 0.7 L/kg . IBW
5.3 <EJT elimination rate constant I; half-life (estimate of elimination rate constant and half-life)
Elimination rate constant (ke) N0 vancomycin I!'QFH $&#F" clearance ?@ volume of
distribution N0$&#'&I-+ '$(-"0 /
ke (hr-1) = Cl/Vd
Y$#'FH(/-&0 !"@.!% 0 Conversion factor N0%(/ time ?@ volume %!F" %"#(J 60 min/hr
?@ 1000 mL/L -!@$(J !FHI+-'$(#@"$& #-(0" " *+&,%!F " vancomycin clearance %"#(J
1.04 mL/min/kg ?@ vancomycin volume of distribution %"#(J 0.7 L/kg $((/I!'QFH elimination rate
constsnt (ke (hr-1)) $& %"#(J (1.04 mL/min/kg . 60 min/hr)/( 0.7 L/kg . 1000 mL/L) = 0.089 hr-1
I'(J Half-life N0 vancomycin (/I!'QFH-"0 .0  $&#F" elimination rate constsnt (ke (hr-1)) %
FH $& Y$I+-'%&#'FHF.0
t1/2 = 0.693/ ke



























































..............................................
14

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

-(0"%- "0 .0#-(0"#'FH ke N&-& I!'Q!FH T1/2 -"0 $& %"#(J T1/2 = 0.693/ ke =
0.693/0.089 hr-1 = 7.8 hr
5.4
 M
pharmacokinetics model I;B2 34 ]7;7 (selection of appropriate pharmacokinetic
model and equations)
!.0J''?JJ IV infusion T' @ 1 hr 1J"'$(JF! N&!N&N0 @.0$!FGHI!J(-  
-! two '.0 three z compartment pharmacokinetic model O#"@(#I/IG$#'J''?@&!FGHI!J(-
 -! twoz compartment pharmacokinetic model '$(JF! N&!N&N0 @.0$@$@0"'$ '^ .0!
#!#'#'-(N0N0# @.0$ ( ./0 .0 (alpha '.0 distribution phase) Y$'!H 30-60 % @(
#I/IG$#'J'' '$(JF! N&!NN0 @.0$F"0d @$@0"&d ?@ elimination rate constant I'(J
I"N0 concentration z time curve ?@*( -!&%#'%N0 -*+&,?-"@' (beta '.0 elimination
phase) I'(J*+&,%!  vancomycin serum concentration- time curve ?JJ three z compartment pharmacokinetic
model 1J"! intermediate distribution phase 1!N/!'"I" alpha ?@ beta N0#' 0" '#^-!Q?!&"
F!'+&?@F! N&@(##'$(#@"#^ IIF(V ?-" .0#"#' 'G#-U&%F@#(/F"0N&% $&
# 1'!F!I@(JO(JO&0%$&FH-}I-'U N&! # N&0 $((/!&@(##'N0 one - compartment
pharmacokinetic model % !"F"0!F!I@(JO(JO&0!#(#!1'H#'FHN$#'&?% !.0'$(JQ
% peak vancomycin serum concentration T@(#'I/IG$N0#'J#'-(N0?@&
#'J'' vancomycin %#'c$ N&@0$ @.0$$ (intravenous) T' @0"&0 1 (Y! '.0
intermittent continuous infusion .0#! half-life %0( #N&0#(J#'' @#'J'' (infusion
time) ?@-&0& @#''0&!#'#'-( $&0"I!J+'HU0#'!H 0.5 z 1( Y! #"0%'$(JQ'$(J%
peak concentrations ?@!JI"%   1?F"I"&0O Q+##($00# T' @ 1.5- 2 (Y!/ ?-"#'
F$I+-''.0I!#'% pharmacokinetic (/1H'! QI"% $&!# '#($00# "' @N0
#'J#' infusion ?@ distribution N0$& .0#! 1?F" @^#&0 %"(/%!# '#($00#  OQ?!&" #'
J'' ?JJ intravenous infusion ?-"#' 0I!#''.0I+-'N0 intravenous bolus !&I!'Q%#'
%'$(J peak concentration N0 vancomycin $&?!"#"?@!F!G"#I@(JO(JO&0%FH-}I-'U%&0
#"   -G*@& clinician !# @.0#& (-'% 7) I!#''.0I+-'N0 intravenous bolus !&#'FH
N$!##"#'&I+-''.0I!#'N0 intravenous infusion #' @.0#&*+&,(/ '$(J%   steady statepeak concentration (Cmax, ss) ?@ steady state- trough concentration(Cmin, ss) Q+# @.0#!&#''(#)*+&,-!
' T% -?" ?@F!'G?'N0#'-$ ./0 0# .0##' @.0#-! infecting organism O steady state version
N0 one-compartment pharmacokinetic model intravenous bolus equation (/$(?I$'@ 0$-'% 9 ?@
10

..............................................
15

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

2034 9 ;<525@9H@12121
4  Vancomycin

Route of administration Single dose
Multiple dose
One-compartment model
Intravenous bolus
C = (D/V). e- ke.t C = (D/V). e- ke.t [(1-e-n.ke.)/( 1- e-ke.) )]

Steady state
C =(D/V) [e- ke.t/( 1- e-ke.) ]

!.0
C F.0 '$(JF! N&!N&N0 H @ t
ke F.0 elimination rate constant
D F.0 N$ (Dose)
n F.0 N0 dose %J''
F.0 Dosage interval
V F.0 volume of distribution
2034 10 @34 pharmacokinetics 34S;<;< 12
4@1H  vancomycin  One-compartment
model
Route of administration Single dose
Multiple dose
Steady state
Intravenous bolus
ke = (ln C1 z lnC2)/(t1- t2)
ke = (ln C1 z lnC2)/(t1- t2)
ke = (ln C1 z lnC2)/(t1- t2)
t1/2 = 0.693/ ke
t1/2 = 0.693/ ke
t1/2 = 0.693/ ke
V = D/Cmax
V = D/(Cmax - Cmin)
V = D/(Cmax,ss - Cmin, ss)
Cl = keV
Cl = keV
Cl = keV
!.0
C1 F.0 '$(JF! N&!N&N0 H @ t1
D F.0 N$ (Dose)
C2 F.0 '$(JF! N&!N&N0 H @ t2
Cl F.0 clearance N0
Cmin F.0 predose trough concentration
ke F.0 elimination rate constant
t1/2 F.0 half-life
Cmax F.0 postdose peak concentration
V F.0 volume of distribution
5.5
 M
;A.<7 ,-7,-J,034 steady-state (steady-state concentration selection)
'$(J Trough concentration % steady-state I!'Q1'H @.0# $&-! -?" ?@F!'G?'N0#'
-$ ./0 0# .0##' @.0#-! infecting organism OY$#-?@&!(#&% therapeutic rang  5-10 mcg/mL
?@#' @.0#'$(JF! N&!N&N0 vancomycin (/ F"0N&!N&0!+@%F@#I(JIG&0 !.0 'J %J#(J
#@G!" aminoglycoside I'(J#'-$ ./0%'G?' '.0% 0(-'Q?#" -(/F'&#''(#)$&#'#$
R!N0'$(J% trough H steady-state  7.5-10 mcg/mL ?% N&0!+@eGJ( $&? &" % steady-state
trough concentration O!F" I+Q 15 mcg/mL 0 !" $&!*@ 1!F! IN0#' #$ vancomycin- induced
nephrotoxicity !##"#'&N$#-% F&#(!?-"0"$ I'(J#'H%*+&, !"-0JI0'.0-0JI0 !"
$10-"0#'&ON$%& trough concentration "#- 01'H 1!N$#'&&I+N/N$%%&
$& trough concentration  15 mcg/mL $& ?@*+&,%! #'-$ ./0-?"%#-"0#' N&QN0 " #'-$
./0 central nervous system 0 -&0 1!F"$(#@"0"'!($'( $& 1.0&I!'Q#($ ./0%  I -GN0
#'-$ ./0 $& ?-" !.0 '"#^-!%! #' @.0#& steady-state trough concentration N0!##" 10 mcg/mL #^F'%

..............................................
16

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

-&0F0-$-!'$(JN0 creatinin clearance N0*+&,0" '%G#( 1.0% $&"%&I!'Q detect

#' #$T nephrotoxicity $& I-(/?-"' '!-&
#'HN0'$(J Peak concentration % steady-state (/ -&0 @.0#'$(J%  110-"0#'%&
I!'Q#' ( H -?"N0#'-$ ./0 $& ?@-&01!@# @'$(J%%& #$0#'N& F##'
& O Y$#-(/N$% !&F.0 20 z 40 mcg/mL ?@#'H%!#'-$ ./0?JJ'G?' '.0% 0(-'Q?#"
- "#'-$ ./0'JJ'I%I"#@(/ '$(J$(#@"/I!'Q 1!N/I+Q'$(J 60 mcg/mL $& ?-" !.0 '"#^
-!%! #' @.0#& steady-state peak concentration N0!##" 40 mcg/mL #^F'% -&0F0-$-!*+&, 
'%G#( Y$ c10"0"$&N0F! 1)-"0+ (ototoxicity; #' $&@$@, '+&I#"!?'$("0+ 1!
!#N/, +0./0, I+V I#'%'-(, $}'), F@. I&, 0 ,  , #'-G# ?@ $ O @"/ -& ) N0
5.6 6 :> C (dosage compute)
&I+-'%&#'FHN$ Vancomycin $(?I$-'% 11
2034 11 Equation used to compute individualized dosage regimens for various routes of administration used
of Vancomycin
Route of administration Dosage interval (), maintenance dose(D), 
loading dose(LD) equation
Intravenous bolus
= (lnCmax,ss - lnCmin, ss)/ ke
D = Cmax,ss V( 1- e-ke.)
LD = Cmax,ss V
!.0
Cmax,ss F.0 maximum concentration % steady state (mg/L)
Cmin, ss F.0 minimum concentration % steady state (mg/L)
ke F.0 elimination rate constant
V F.0 volume of distribution
6.
:.,JA`A1-;A.1J MA
#' @.0#N$ (dose), "' @N0#'J'' (dosing interval) '.0#'FHN$&?#"*+&,
$(%#@"!?@&%(/ 5 S(/  1?F"#''!H'.0F$ $ N$ (dose), "' @N0#'J''
(dosing interval) $&#'0&0#*@#'}#)#@G"!'#'%( d  O#*@N0#'&*+&, !"  -!
F!F$(%(/$&'I%ST1 ?@0#'1)##'& 0 -&0!#'-$-!($'$(J @.0$ 1.0!
'(J @N$#'&!"&?#"*+&,?JJ c1' Y$ !.0!N&0!+@N0'$(J @.0$N0*+&,?@& #^I!'Q
!&'(JN$$&S#'-"d OS% %!!0+" @S$& #($('@ 0$$(-"0 /
6.1 Sawchuk-Zaske method
@(##'IF(VN0S#'FHN$$&S$( #@"/ $&?#"
1. S$(#@"/& one-compartment model #'FH pharmacokinetic parameter ?@ dosage
regimen

..............................................
17

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

2. peak concentration F.0 '$(J% $&##' ($'$(J @.0$% @ 1-3 (Y! @(##'&
 I'^?@& 1.0&*"" distribution phase #"0 ( 1.0&I0$F@&0#(J#'& one-compartment
model)
3. '$(J @.0$'" distribution phase (/ !"!F!IF(V
4. therapeutic rang N0 peak concentration F'- #"% F& (30-40 mg/L) "F'  20-30 mg/L
-&
5. @N0#'  @.0$F' !I!%?@*@ pharmacokinetic parameter $&
0" '#^-! Q?!&" S$ (#@"/& $&$#''(JN$ ?-"F!Q+#-&0N0F" Pharmacokinetic
parameter % $& " clearance '.0 Vd % $&#^0 !"!F!Q+#-&0(# I'(J#'&S$( #@"/-&0&'$(J @.0$
0"&0 2 '$(J O!(# @.0#& peak ?@ trough concentration ?@&!FH-!N(/-0?I$'@ 0$
-'% 12
2034 12 1W
@1H G;1
4 Sawchuk-Zaske method
@$(J% N(/-0#'FH
I+-'%&
1
FH elimination rate constant (ke) ?@
ke = (ln C1 z lnC2)/(t1- t2)
elimination half-life
t1/2 = 0.693/ ke
2
FH Vd
Vd = R0/ ke. {(1- e-ke.t)/[Cmax- (Cmin . e-ke.t)]}
3
@.0#F" peak concentration %-&0#' (Cmax,D) ?@ = t + (-1 / ke) . ln (Cmin,D / Cmax,D)
trough concentration %-&0#' (Cmin,D) 1.0F"
dosing interval %F' 
4
 infusion rate (R0) ?@ dose N0 vancomycin % R0 = ke. Vd . Cmax,D . [(1-e-ke.)/( 1- e-ke.t)]
!I! 1.0& $& peak ?@ trough concentration Dose (mg) = R0. t
-!-&0#'
5
% peak concentration (Ct, max) % @ t @(& Cmax = (R0/ ke.Vd) . [(1- e-ke.t)/ ( 1- e-ke.)]
 I'^ ?@ trough concentration (Cmin) % $&# Cmin = Cmax . e-ke.(-t)
dosage regimen !"
!.0
C1 F.0 '$(JF! N&!N&N0 H @ t1
C2 F.0 '$(JF! N&!N&N0 H @ t2
ke F.0 elimination rate constant
t1/2 F.0 half-life
Vd F.0 volume of distribution (L)
R0 F.0 infusion rate (mg/hr)
F.0 Dosage interval
t F.0' @#'J'' (infusion
period; hr)

D F.0 N$ (Dose)

Cl F.0 clearance N0
Cmin F.0 true trough concentration (mg/L)
Cmax F.0 true peak concentration (mg/L)
Cmax, D F.0 peak concentration %-&0#'
(mg/L)
Cmin, D F.0 trough concentration %-0& #'
(mg/L)

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18

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

6.2 Propotional dosage adjustment

S$(#@" / S# ''(JN$-!I($I"N0'$(J @.0$%-&0#''(J !.0QT Steady state ?@&
Y$ !.0%'J '$(J% peak concentration ?@ trough concentration % $&##' ($'$(J-! @N0#'
% !I! F.0 Peak % 15-30 min @(& I'^ ?@ Trough F.0 #"0&!./0Q($  #^I!'Q!FH 1.0&
$& F"I($I"$&#' %J#(JN$ $!%& 0(I!'Q%& $&!O N$!"%F $"&'$(J peak
concentration ?@ trough concentration !"-!%- &0#' $& 0" '#^-!S# '$(#@"/ !" $&!#'&#'FH
##(J pharmacokinetic parameter N&! #N&0?-"0"$
(Cpeak, ss z Ctrough, ss)/ Dose = (Cpeak, D z Ctrough, D)/ New dose
!.0

Cpeak, ss F.0 peak concentration % steady state (mg/L)

Ctrough, ss F.0 trough concentration % steady state (mg/L)
Cpeak, D F.0 peak concentration %-&0#' (mg/L)
Ctrough, D F.0 trough concentration %-&0#' (mg/L)
Dose F.0 N$ $!%%  & $&'$(J%  ($ (%(/ peak ?@ trough)
New dose F.0 N$!"%- 0& #'

6.3 Bayesian forcasting method

S%-&0& Program F0!1 -0'U O &@(##'-! two- compartment model ?@#''!H population
parameter O#''(JN$#'&(/I!'Q&'YU $&#'$(J @.0$ 1 '.0 2 '$(J%IT steady state
'.0 !"#^ $&!&#'FH
Vancomycin monitoring
!"?&!#'-$-!-'($'$(J vancomycin  routine .0#!@(#%#'&0%
I(JIG 0#%(/( !"!F!($  ##(J"T nephrotoxicity ?@ ototoxicity N0I!'QR0#( $&$&#'-$
-!"'$(JF! N&!N&N00" N&!$ I'(J#'H%! #'#'-$-!-'($'$(J(/ !"?&%#'-'
($'$(J%  Peak (post) levels %(//%(/(/ .0!# !FGHI!J(-   time-dependent (time > MIC) killing !#
#"% !FGHI!J(-  concentration-dependent killing, !#'#'-( I+" peripheral tissues & %&#-"0#'
 F'U Peak (post) levels $&0"?!"?@Q+#-&0, ?@'$(J%   Peak (post) levels (/ !" $&!F!I(!1(SU#(
#(J#'$N/% clinical outcome N0*+&,
I'(J#'-$-!0#'%F@# *@#'-0JI0-"0#''(#) 0#'1)'.00#'N& F##'&0.d
(/?I$'@ 0$$(-'% 13

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19

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

2034 13 Monitoring plan H2 vancomycin

Baseline and follow-up monitoring parameter
Baseline
Follow-up
0G, 1},I"I+
/(#
( &(
0GHT+!'"#
tid
BUN, Cr
%G# 3 (
CBC (with differential)
%G# 3 (
Culture and Sensitivity tests
(% 2-4 N0#''(#)
Fluid intake/output
%G#(
0.%&'" !
%G#(
0.%!1) -"0+?@ %G#(
IJ"/*@#''(#)?@1)N0
%G#(

Tc=1J
8
>T 8M42
A272>A;A. (Trough Concentration)
1. *+&,!IT#'%N0 -% !"F% (unstable renal function)
2. *+&,0&%!IGNT1 (> 190% IBW) !"F"0?N^?'$ (FH trough concentration 3
52 5
dose ;< 2)
3. *+&,% $&'(J#''(#)$& vancomycin !!##" 2 I($U
4. *+&, $^#'.0%'#O!#'-$ ./0%'G?'
5. *+&,%!T cerebrospinal fluid shunt infections ?@ meningitis
6. *+&,%! clearance N0%'$ '^ " *+&, cystic fibrosis, burns > 20% BSA -&
7. *+&,%% dialysis J' T% " high flux and continuous arteriovenous hemodialysis/filtration
(CAVH)] ?-"I'(J#'HN0*+&,%% dialysis ?JJ Continuous ambulatory peritoneal dialysis
(CAPD) ?@ conventional hemodialysis (/ !" -&0!#'-$-!-'($'$(J  routine
.0!#" #'% dialysis ' T%$(#@"(/ !" $&%&!# 'I+V I00# ##'?I @.0$?-"0"
$

2
A27 (Monitoring)
Serum creatinine !'@ 0$ ##(J#'-$-!$(/
1. #"0#' $&'(JF'!#'-'($ Baseline Serum creatinine #"0
2. T@(##' '! $&'(J ?@&F'!#'-$-!%G#d 1 I($U '.001'H-$-!
-'($J"0N/ $& !.0 !#' @ ?@N0 renal function '.0 !.0 $&'(J0.d %!F! 
nephrotoxicity " $#(



























































..............................................
20

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

3. !.0!#' @?@N0F" Serum creatinine #^F'!#''(J @N$& !I!-!

dosing interval %?
Vancomycin trough level !'@ 0$ # #(J#'-$-!$(/
1. 1'H-'($'$(J-! #HwU$(%#@"!?@&
2. #' #^J-(0" @.0$(/F' #^J% @&0#"'.0 %"#(J 30 %#"0#'&*+&, $&'(JF'(/
Q($ 
3. F!QN0#' #^J-(0" @.0$F.0
- level ?'# H steady state (dose % 3-5)
- F'(/Q($ %G#d I($U (I($U@ 1 F'(/ '.00 1!F!Q! #N/ !.0!#'
@?@N0 renal function '.0 !.0 $&'(J0.d %!F!  nephrotoxicity
" $#()

I:e,0;A. (Interpretation of Trough Level)
Therapy
Measured Trough Level (mg/L)
<5

Vancomycin
5 - 15
5 - 15
> 20
<5

Vancomycin + aminoglycoside
5 - 10
10 - 20
> 20

Dosing Interval Adjustment

- Q&*+&, on 0+"%!##"%G#d 24
(Y! &@$ interval @0#12
(Y!
- Q&*+&, on 0+"%%G#d 12 (Y!
F'-&0N0F'#)%
pharmacokinetic
!"-&0!#' @?@
1! interval N/0#12 (Y!
F'-&0N0F'#)%
pharmacokinetic
- Q&*+&, on 0+"%!##"%G#d 24
(Y! &@$ interval @0#12
(Y!
- Q&*+&, on 0+"%%G#d 12 (Y!
F'-&0N0F'#)%
pharmacokinetic
!"-0& !#' @?@
1! interval N/0#12 (Y!
F'-&0N0F'#)%
pharmacokinetic

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  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

:A<9 1  # 0G 50  /(# 70 kg I+ 178 cm (70 /) !?*@-$ ./0 MRSA *@#'-' Scr= 0.9 mg/dL 5 (
#"0#' N&! admiss !T stable $ # @.0#& vancomycin *+&,'/ *+&,F' $&'(JN$ %" ' (no
acute distress, normal Temp, WBC 1!N/ @^#&0, ?*@ warm ?@?$ ! discharge @^#&0)
1. FH creatinin clearance N0*+&,



































































































.
2. FH vancomycin clearance




































































































3. FH volume of distribution


















































4. FH elimination rate constant ?@ half-life



































































































.
5. @.0#'$(JF! N&!N&N0% steady-state %-&0#'
Cmin, ss 









. mcg/mL
Cmax,ss 









..mcg/mL
6. FH Dosage interval (), maintenance dose(D)
6.1 =












































..
6.2 D =












































..
7. FH?@ loading dose(LD) equation (# -&0&)



































































































.

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22

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)

g :A<9 1

1. FH creatinin clearance N0*+&, Y$ @.0#& Cockcroft-Gault method 1'*+&, !" $&0&
CrCl = [(140-0G). BW]/ (72.Scr) = [(140-50).70]/ (72.0.9) = 97 ml/min
2. FH vancomycin clearance
Cl = 0.625(CrCl) + 0.05 = 0.625(97 ml/min/70 kg) + 0.05 = 1.013 ml/min/kg
3. FH volume of distribution
V = 0.7 L/Kg. 70 kg = 49 L
4. FH elimination rate constant ?@ half-life
ke (hr-1) = Cl/Vd = [(1.013 ml/min/kg). 60 min/hr]/ ( 0.7 L/kg . 1000 mL/L)= 0.087 hr-1
t1/2 = 0.693/ 0.087 hr-1 = 8 hr
5. #' @.0#'$(JF! N&!N&N0% steady-state %-&0#'
.0#T#'HU-$ ./0*+&, ( ?JJ c1% ?@( !"'G?'!# $((/ @.0# Cmin, ss  7
mcg/mL ?@ Cmax,ss  20 mcg/mL
6. FH Dosage interval (), maintenance dose(D)
6.1 = (lnCmax,ss - Cmin, ss)/ ke = (ln 20 mcg/mL z ln 7 mcg/mL)/ 0.087 hr-1 = 12.1 hr (rounded 
12 hr)
6.2 D = Cmax,ss V( 1- e-ke.) = 20 mcg/mL . 49 L ( 1- e-(0.087 hr)(12 hr)) = 635 mg (should be rounded to
the nearest 100 to 250 mg) #'H case / rounded  750 mg
7. FH?@ loading dose(LD) equation (# -&0&)
1'HFH loading dose !.0*+&,! CrCl &0#" 60 mL/min O*+&,'*/ +&,#^ !"
 -&0 $& loading dose 1' CrCl = 97 ml/min

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23

 
   
  Vancomycin (Clinical Application and Pharmacokinetics of Vancomycin)


1. Katzung BG, ed. Basic and clinical pharmacology, 8th ed. New York: Lange medical books/McGrawHill; 2001.
2. MICROMEDEX Healthcare Series DRUGDEX Drug DEX evaluation [online]
3. Wilhelm MP, Estes L: Vancomycin. Mayo Clin Proc 1999; 74:928-935.
4. Centers for Disease Control and Prevention. Recommendations for preventing the spread of
vancomycin resistance: recommendations of the Hospital Infection Control Practices Advisory
Committee (HICPAC). MMWR 1995;44(No. RR-12): [3-5].
5. Bauer, Larry A. Applied Clinical Pharmacokinetics. McGraw-Hill. 2001
6. Evans W, Schentag J, Jusko J (eds): Applied Pharmacokinetics 3rd edition. San Francisco, CA.
Applied Therapeutics, 1992.
7. W!@ '. #'-$-!-'($'$(J vancomycin. : 0T'H F ?@ GT1' '#G@,
J''HS#'. #'-$-!-'($'$(J @.0$. N0?#". TF TI(#''!F@# FH TI(}I-'U
!%@(N0?#", 2543: 57-69.

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24