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ANNALS O F C L IN IC A L A N D LABO RA T O RY S C IE N C E , Vol. 6, No.

3
Copyright 1976, Institute for C linical Science

Drug Interference in Laboratory Testing

D O N A LD T. FORM AN, Ph.D .*


and D O N A LD S. YOUNG, M.B., P h.D .f
*D epartm ent o f Pathology i? Laboratory M edicine,
E vanston H ospital,
E vanston, IL 60201
and
\Clinical Center,
National Institutes o f Health,
Bethesda, MD 20014

ABSTRACT
C haracteristic problem s in th e interpretation of laboratory data w h en a
drug or its m etabolite interferes w ith a laboratory procedure are review ed.
Various m echanism s of interference (physical, chem ical, pharm acological
and drug-drug interaction) are discussed. T he role o f a com puterized drugtest interference file in assisting in th e prediction as w ell as interpretation
of apparent test results is described.
Introduction
tic le on th e ch em ical an d d iag n o stic
O ver th e past decades, the practice of specificity of laboratory tests. In 1964,
m ed icin e has u n d erg o n e con sid erab le B orushek and G old 1 published an article
sophistication. P otent new drugs in prac containing a list of drugs interfering w ith
tically every therapeutic category are avail routine endocrine procedures. W irth and
able. W henever a patient receives a T hom pson ,19 in 1965, pu blished a list o f
drug, there is a possibility of drug-test in substances and conditions w hich affect
terferences. W hen m ore than one drug is th e re su lts o f lab o rato ry p ro c e d u re s.
adm inistered, th ere m ay also be drug- T hey included such factors as tem pera
drug interactions. T hese developm ents ture, light and drugs. O ther review artih av e c re a te d n ew p ro b le m s for th e cles 8,11,14,17 have b een of great value in
laboratory scientist. A characteristic prob helping to define this problem .
O ne of the m ost am bitious approaches
lem is th e in terp retatio n o f laboratory
to
this problem has b een the develop
data w hen a drug or its m etabolite may
m
ent
of a 9000-entry com puter-file based
in terfere w ith a laboratory proced ure.
O ne drug m ay affect the action o f another on a compilation of 1030 literature refer
given at the same tim e, thus changing the ences .20 This com puterized com plication
of effects of drugs on laboratory tests has
value of a test result.
N um erous attem pts have b een m ade b een used to assist in th e interpretation
by a num ber of com pilations and articles o f u n u su al te st resu lts in th e clinical
to d o c u m e n t th e s e effe c ts. In 1962, chem istry laboratories of th e N ational In
Caraw ay 2 pu blished a com prehensive ar stitutes of H ealth and the E vanston Hos263

264

FORMAN AND YOUNG


TABLE I

Colored Urines Due to Drugs or Metabolic Disorders

Color o f Urine

Orange-red

Red

Cause

Phenazopyridine
Phenindione
Phensuximide
Porphyrins

Red-brown

Hemoglobin and
derivatives
Urobilin

Yellow
Green-yellow

Chloroquine
Bile pigments

Blue
Blue

Methylene blue
Triamterene
Indigo compounds

Blue-green
Brown-black

Aiaitripty 1ene
Melanin
Homogentisic Acid

Disorder

Drug related

Congenital
porphyria
Acute
intermittant
porphyria
Crush
syndrome
Hemolytic
anemia
Drug related
Regurgitative
jaundice
Drug related
Intestinal
disease
(indicanemia)
Drug related
Malignant
melanoma
Alkaptonuria

pital of N orthw estern U niversity M edical


C enter, as w ell as in som e other centers.
A major problem facing users of the
various collations of laboratory test inter
ferences is the relationship betw een drug
dosage and diagnostic test interference
and the possible synergistic effect of sev
eral drugs. T he m etabolic and clinical
states of the patien t also affect the degree
of laboratory in terferen ce. If an in d i
vidual has norm al kidney and liver func
tion, the response w ill be different to a
drug dosage than that of th e patien t w ho
is unable to detoxify or to excrete the
com pound.
In order to cope w ith the problem of
drug induced m odifications of laboratory
test values, laboratory scientists should
possess an understanding of th e m ech
anism s involved in these interferences.
T he purpose of this article is to consider
these m echanism s and to discuss the role
of the com puterized drug-test interference
file in the prediction as w ell as the inter
pretation of apparent test results.

M echanism s of Interference
T here are four distinct m echanism s of
interference in laboratory testing. Physi
cal, c h e m ic a l, p h a rm a c o lo g ic a l an d
drug-drug interactions are of special in
te re st to th e lab orato ry scien tist. T he
m echanism s of th e interferences w ill be
briefly review ed and, w herever possible,
solutions suggested.
P h y s ic a l E f f e c t s

D rugs may interfere w ith colorim etric


photom etric or fluorom etric analyses by
im parting a characteristic color to the
specim en. In table I are described som e
unusually colored urines and their rela
tio n sh ip to d ru g a d m in istra tio n or
m etabolic disorders. T his type of inter
fe re n c e can b e d e te c te d v isu a lly by
laboratory person nel and drug interfer
ences may be circum vented by collecting
th e specim en after an appropriate length
of tim e during w hich th e drug in question
has b een discontinued. T here are m any
v arieties o f drugs an d foods th a t can
cause th is ty p e of in terference. T h ese
should be co n sid ered first as possible
causes of any unusually colored urine.
Som e drug s act as in d icato rs (e.g.,
p h e n o lp h th a le in , v eg etab le laxatives)
and affect tests carried out at a particular
pH . T he p resence of sulfobrom ophthalein dye (BSP) in serum w ill interfere
w ith serum protein determ in ed by the
b iu ret m ethod. T h e dye is colorless at the
pH of blood b u t pu rp le w hen m ade al
kaline during th e assay.
C h e m ic a l E f f e c t s

D rugs m ay b e m easured as analytes,


e ith e r b e c a u se o f th e ir sim ila rity in
chem ical structure or because they con
tain a com ponent th at is an analyte. P a
tients w ho have receiv ed radiographic
con trast m ed ia co n tain in g io dine w ill
have an altered protein-bound iodine, al
though thyroxine is not affected w hen d e
term in ed by protein bin d in g m ethods.
T he m ost serious and long-lasting inter
ferences are those caused by intraven

DRUG INTERFERENCE IN LABORATORY TESTING

ously adm inistered iodinated radiopaque


agents (e.g., acetrizoate and adipiodone).
T he drugs orabilex and dionsil have a
negligible effect on th e analysis of pro
tein b o un d iodine at a concentration no
greater than 100 fig p er dl, b u t seriously
affect the procedure at 1000 fig per dl.
Serum potassium concentration is in
creased by the concurrent adm inistration
of intravenous potassium penicillin G.
T he penicillin preparation contains 1.7
m m ol o f potassium per m illion units.
Thus, a patien t receiving 10 m illion units
of th e antibiotic receives 17 m m ol (m Eq)
o f potassium .
A chem ical interference m ay also result
w hen the substance b eing determ ined
reacts in vivo w ith a drug adm inistered
prior to th e collection of blood for
analysis. F or exam ple, serum calcium de
term inations m ay be affected by the ad
m in istratio n of th e ch elatin g agent,
ethylenediam inetetracetate (ED TA ).3 In
certain conditions such as lead poisoning
and collagen disease, E D T A has b een
used therapeutically to reduce th e lead
and calcium concentrations, respectively.
Less w ell recognized is th e fact th at vari
ous chelating agents are also used as p re
servatives to p reven t oxidation reactions
in drug preparations. In patients on
ED TA therapy, calcium cannot be de
term ined by the indirect colorim etric or
fluorom etric m ethods based on th e chela
tion o f a calcium E D T A com plex. H ow
ever, in calcium d eterm in atio n s by
ato m ic-ab so rp tio n sp ectro sco p y , th e
com plexing agent is destroyed in the
flam e and th e direct concentration of cal
cium can be determ ined.
D rugs can also interfere w ith labora
tory results by negating certain non
specific oxidation and reductions essen
tial for the chem ical assay. Penicillin,
strep to m y cin an d ascorbic acid are
know n to react w ith cupric ion; thus, false
positive results for glucose may occur if a
copper reduction m ethod is used. If the

265

sp e c ific e n z y m a tic g lu co se-o x id ase


m ethod is em ployed, ascorbic acid can
cause a false negative result by preven t
ing the oxidation o f a specific chrom ogen
in the reaction.
Increased transam inase activity has
been observed w hen the diazocolorim etric m ethod is used. U nusually increased
activity has b een reported in patients
w ith ketosis and also in patients receiv
ing erythrom ycin 13 or p-am inosalicylic
acid .9 T hese test interferences can be ob
viated by em ploying ultraviolet kinetic
procedures.
C olorim etric procedures u sed in steroid
assays are often subject to drug interfer
e n ce . In th e d e te rm in a tio n o f 17ketosteroids by th e Z im m erm an reaction,
drugs w ith th e 17-keto basic structure,
such as ascorbic acid, m orphine and reserpine, w ill cause increased values. In
th e determ ination of 17, 21-dihydroxysteroids by the Porter-Silber reaction, the
dihydroxyacetone chain is th e reactive
unit. D rugs like m eprobam ate, chloral hy
drate, chlorprom azine and potassium io
dine w ill interfere w ith this reaction and
cause elevated values. In the colorim etric
determ ination of vanillylm andelic acid
(VMA) by a diazo reaction, drugs like
m ethocarbam ol and m ethyl dopa cause
falsely elevated results.
W hen specific drugs have b een dem
onstrated to interfere w ith chem ical
reactions, patients should be m aintained
free of these drugs for at least 72 hours
before collecting the specim en. O ther
an aly tical te c h n iq u e s, e.g ., co lu m n
chrom atography and radioim m unoassay
procedures, can also be subm itted for an
affected m ethod.
Pharm acological Effects
This type o f interference usually re
sults from the pharm acological or toxic
activity of drugs b u t m ay also arise from
th erap eu tic q u an tities of drugs. An
exam ple is the increase in prothrom bin

266

FORMAN AND YOUNG


TABLE II
Drugs Capable of Increasing Blood Glucose

Dextrothyroxine
Diazoxide
Diphenylhydantoin
Diuretics
Nicotinic acid

Phenothiazines
Steroids
Adreno cort icos teroids
Estrogens
Sympathomimetic amines

TABLE III
Drugs Capable of Decreasing Blood Glucose

Alcohol
Asparaginase
Caffeine
Haloperidol

Monoamine oxidase inhibitors


Propoxyphene
Propranolol
Anabolic agents

tim e w hich results from th e adm inistra


tion of a therapeutic am ount of sodium
w arfarin. H ow ever, unexpected interfer
ences resulting from side effects or ad
verse reactions may create problem s in
the interpretation of laboratory data. D is
turbances in fluid and electrolyte balance
a n d h y p o p o ta sse m ia are com m on.
T hiazide diuretics and large doses of
glucocorticosteroids may severely reduce
th e concentration of plasm a potassium .
A cetazolam ide and ethoxazolam ide m ay
cause m etabolic acidosis, raised serum
uric acid and low ered urinary excretion
of uric acid. A rise in serum uric acid has
also b een reported follow ing the ad
m inistration of levodopa .4 T he thiazides
can also have a hyperglycem ic activity
TABLE IV
Hormone Levels in Women on Oral Contraceptives*

Level in
Menstruating
Women

Plasma cortisol 15.0 4.0 yg/dl


(8:00 A.M.)
Serum thyroxine
6.6 1.4 yg/dl
Urinary 17-OH
4.6 1.1 mg/d
corticosteroids
Estrogens, total 40.0 18 yg/d
(urine)
Vanilmandelic
3.5 1.6 mg/d
acid (urine)

Level in Women
on Oral
Contraceptives

40.0 11 yg/dl
9.4 1.7 yg/dl
2.6 0.9 mg/d
26.0 7.4 yg/d
3.3 1.6 mg/d

*Lucis, O.J. and Lucis, R. : Bull. WHO 46:443, 1972.

and diabetics m ay require m ore insulin


or oral antidiabetic drugs. Patients w ith
latent diabetes occasionally develop an
abnorm al glucose tolerance curve. Salicy
lates have also b een reported to reduce
hyperglycem ia in diabetics and produce
hypoglycem ia in norm al children. In ta
bles II and III are listed various drugs
capable of increasing or decreasing blood
glucose in non-diabetic subjects.
H ydantoin anticonvulsants m ay cause
th e appearance o f positive lupus erythem
atosus (L.E.) cells and m ethem oglobin
em ia. C hlorprom azine has also been
im plicated in causing a syndrom e like
system ic lupus erythem atosus w ith accom paning positive tests for L.E. cells and
antinuclear antibodies .6
In m any instances, adm inistered drugs
alter a m etabolic pathw ay and directly
produce changes in biochem ical values.
Insulin adm inistration results in changes
in blood glucose, potassium , phosphorus
and fatty acids. A llopurinol reduces uric
acid by in hibiting th e enzym e, xanthine
oxidase; other drugs, e.g., azoserine and
m ethotrexate, do so by preventing its
biosynthesis. H ydrochlorothiazide in
creases uric acid retention by decreasing
its tu bu lar excretion. Oral contraceptives
have a m arked effect on plasm a glucose,
fatty acids and grow th horm one levels .16
E strogen-progestin oral contraceptives
produce increases in serum iron, ironbind ing capacity, transferrin, ceruloplas
m in and cop per .18 T hese effects on en
docrine functions are qu ite m arked as in
dicated by m easurem ent of the related
biochem ical constituents (table IV ).12
Som e drugs induce unexpected side ef
fects un related to th eir therapeutic ac
tions. Inheritance of hem oglobins differ
ing in structure from norm al hem oglobin
A is w ell described. All types of hem o
globin are oxidized to m ethem oglobin by a
w ide range of agents and about 1 percent
o f hem oglobin present in the blood of
norm al peo ple is in this form. M any drugs

DRUG INTERFERENCE IN LABORATORY TESTING

267

TABLE VI
slightly increase th e am ount of m ethem oDrugs Inducing Hepatic Microsomal Enzymes
globin, even in norm al individuals, b u t
induce a striking and som etim es fatal
Barbiturates
m ethem oglobinem ia in susceptible pa Phenylbutazone
Glutethimide
Cortisone
Chlordiazepoxide
tients. T hese drugs include chlorates, Aminopyrine
Testosterone
sulfonam ides, nitrites, quinones, acetan- Diphenylhydantoin
Norethynodrel
Carbutamide
ilid and acetophenetidin. A sim ilar p h en
om enon occurs w ith prim aquine sensitiv
ity. Susceptible patients have an in herited tisol and decrease the concentration of
defect in red cell glucose 6 -phosphate de cortisol in th e plasm a.
A dverse side reactions m ay also occur
hydrogenase (G 6 -PD ) an d develop a se
w
ith
pharm acologically active drugs.
vere hem olytic anem ia w hen exposed to
M
any
drugs have b een associated w ith
prim aquine.
inducing
abnorm al liver, renal an d p u l
A nother abnorm al drug response is
m
onary
function
.10 T hese drug-test ef
porphyria. A cute porphyria on exposure
fects
are
unexpected
and should be rec
to drugs can be caused by sudden m as ognized. D rugs in this
group include
sive induction o f deltaam ino levulinic m ethyltestosterone, reserpine,
phenaceacid synthetase in hepatic m itochondria
m
ide,
oxyphenylbutazone,
anesthetics
w hich results in uncontrolled form ation
a variety of cancer chem otherapeutic
of porphobilinogen and its m etabolites. and
agents.
S usceptibility is in herited as an au
tosom al dom inant trait and occurs even in D rug-D rug Interactions
heterozygotes. T he nature o f th e m olecu
D rugs w hich in dep end ently have little
lar defect is unclear and presum ably lies effect on laboratory tests m ay interact to
in the repression m echanism for the gene produce a significant alteration o f test
controlling form ation of the enzym e pro values. In table V II are presented several
tein. E xposure to any o f the drugs listed drug interactions in diabetic hum an sub
in table V results in further m arked dere jects w hich can affect an apparent test
pression of enzym e synthesis and severe result .15
porphyria.
T he adm inistration of clofibrate to a p a
In table VI are listed several drugs in tien t taking warfarin w ill potentiate the
ducing hepatic m icrosom al enzym es .5 anticoagulant effect of w arfarin by dis
T hese enzym es can m etabolize th e drug placing it from its protein bind ing site .7
as w ell as other substrates. Barbiturates, T his interaction w ill cause a significant
griseofulvin and glutethim ide induce en increase in the prothrom bin tim e test
zymes w hich m etabolize coum arin and used to regulate w arfarin adm inistration.
p h enindion e derivatives and thus reduce D isplacem ent o f drugs from th eir b inding
th eir anticoagulant activity. D iphenylhy- sites is a com m on m echanism by w hich
dantoin and phenylbutazone stim ulate drug-drug interactions result in unex
cortisol hydroxylase activity and increase p ected laboratory data. After absorption,
the urinary excretion of B-hydroxy cor- about 50 to 80 percent of salicylate is
bound to serum album in, from w hich it
T ABLE V
d isp laces o th e r su b stan ces such as
Drugs Inducing Marked
bilirubin
and thyroxine. O ther drugs such
De-repression of Enzyme Synthesis
as coum arin may also be displaced w ith a
sudden change in prothrom bin tim e.
Chloroquine
Diallybarbiturate
Aminopyrine
Allylisopropylacetylurea
D rug-drug interactions m ay also cause
Sulfonamides
Hexachlorobenzene
enzym e induction. Ethchlorvynol, glu-

268

FORMAN AND YOUNG


T A B L E VII
Drug Interactions Reported in Diabetic Subjects

Drug Interaction

Hypoglycemic Drug

Alcohol

Insulin
Sulfonylurea
Phenformin
Chlorpropamide
Insulin
Insulin
Insulin
Insulin

Alcohol
Bishydroxycoumarin
Guanethidine
Oxytetracycline
Phenothiazine
Propranolol

Reaction

Inhibition of gluconeogenesis
Lactic acidosis
Decrease in excretion or metabolism of hypoglycemic agent
Decrease in insulin dosage needed to control patient
Decrease in insulin dosage needed to control patient
Increase in insulin dosage needed to control subject
Decrease in insulin dosage needed to control subject

tethim ide and haloperidol are know n to


in h ib it the effectiveness of w arfin therapy
by this m echanism .7 T hese drug-drug
interactions may result in a redic ed protlr on b in tin e. E nzyn e inhibition is
another resu lt of drug-drug interaction
an d the in paim e n t of the hepatic glicur onyl transferase system by phenothiazine
derivatives is a good exam ple. W henever
several dru gs are adn in istered c oncug
rently to a patient, th eir com bined effect
on laboratory results should be carefully
considered.
E ffectiveness of C om puterized D rug
Interference F ile
T he com puterized drug interference
file has b e e n used in tw o m odes. In one,
possible interactions are listed in re
sponse to direct queries (the role for
w hich it was originally designed). In the
other, th e file has been used to provide
autom atic interpretation of effects of
drugs on tests. In this m ode, the file is
used to provide a report alerting a physi
cian to a possible interaction betw een a
drug and a test (figure 1). W ithout a com
puterized hospital inform ation system,
w hich could be accessed to provide in
form ation about a patien ts clinical state
and nontherapeutic-drug procedures, the
drug file cannot be com pletely effective
in providing explanations for changes in
laboratory data. Its role m ust be that of a
w arning system to highlight possible
causes o f changes in test values w hich

can be accepted or rejected b y the pa


tien ts physician on th e basis of his clini
cal ju d g m en t
O ur experience in a university teaching
hospital, in w hich over 10,000 patientdays w ere m onitored, indicated th at the
drug file provided the correct explanation
for changes in laboratory data in approx
im ately 21 p ercent of all the occasions in
w hich a report was produced .21 A report,
sim ilar in con ten t and form at to an entry
in the m aster file ,20 was generated w hen
an abnorm al test resu lt was produced and
one of th e adm inistered drugs had b een
described as causing th e effect. T he yield
of correct explanations w ould undoub
tedly be increased by elim ination of ef
fects th at w ere unlikely to arise in hospi
tal practice, e.g., effects ow ing to over
doses or toxic effects of drugs. To m ake it
appropriate for on-line use in any particu
lar hospital, the file should be m odified
to elim inate these effects. T he only
m ethodological interferences that should
be in clu ded are those involving the pro
cedures in use in the hospital laboratory.
T he file is being m odified for use in the
autom atic w arning role in a com m unity
hospital to determ ine if it can provide a
useful service for physicians w ith a differ
ent orientation from those in a university
hospital.
In the off-line m ode of use of the drug
file, the data-base, stored in a tim e-shared
com puter, is interrogated through a re
m ote device such as a cathode-ray term i-

DRUG INTERFERENCE IN LABORATORY TESTING


DRUG EFFECTS
PATIENT ID.
PATIENT NAME
ROOM NUMBER
DOCTOR

DRUG:

10/23/75
086-24-095
ROBERT STAR
4102
GUTHRIE

HEPARIN

BLOOD
CLOTTING TIME INC
CONCENTRATION RELATED EFFECT

(WHOLE)

PHYSIOLOGICAL EFFECT
REF:
0704

BLOOD

(WHOLE)

PHYSIOLOGICAL EFFECT
REF:
0384

FACTOR V DEC
BLOOD
CONCENTRATION RELATED EFFECT

(WHOLE)

PHYSIOLOGICAL EFFECT
REF:
0384

BLOOD
FACTOR XI DEC
CONCENTRATION RELATED EFFECT

(WHOLE)

PHYSIOLOGICAL EFFECT
REF : 0384

PLATELET COUNT DEC


BLOOD
(WHOLE)
REPORTED EFFECT FOLLOWING I.V. INFUSIONS

PHYSIOLOGICAL EFFECT
REF:
0656

PITT INC
BLOOD
CONCENTRATION RELATED EFFECT

(WHOLE)

PHYSIOLOGICAL EFFECT
REF : 0704

THROMBIN TIME INC


BLOOD
(WHOLE)
RELATED TO CONC OF CIRCULATING HEPARIN

PHYSIOLOGICAL EFFECT
REF:
0704

THROMBOPLASTIN GEN DEC


BLOOD
ABNORMAL RESPONSE (INHIBITION)

PHYSIOLOGICAL EFFECT
REF : 0384

FACTOR IX DEC
REPORTED EFFECT

F igure 1. Report alertingphysicianto druginterferences in laboratory test


ing.

269

(WHOLE)

AMMONIA INC
PLASMA
CONTAINS VARIABLE AMOUNTS OF AMMONIUM SALTS

ANALYTICAL EFFECT
REF:
0181

CORTICOSTEROIDS INC
PLASMA
IF CONTAMINATED BY IMPURITIES

ANALYTICAL EFFECT
REF:
0524

INSULIN DEC
PLASMA
EFFECT IN HEPARINIZED PLASMA AND SERUM

ANALYTICAL EFFECT
REF:
0709

INSULIN INC
PLASMA
SPURIOUSLY HIGH VALUES REPORTED FOR IMMUNOASSAY

ANALYTICAL EFFECT
REF : 0064

PROTHROMBIN TIME INC


PLASMA
CONCENTRATION RELATED EFFECT

PHYSIOLOGICAL EFFECT
REF : 0704

TSH DEC
PLASMA
INTERFERES WITH THYROXINE BINDING TO PROTEIN

PHYSIOLOGICAL EFFECT
REF:
0502

nal. T he questions th at may be asked in


clude all the effects of a drug, all the
drugs that affect a test or, m ore specifi
cally, does a particular drug affect a par
ticular test procedure by a particular
m echanism . In each of these situations it
is possible to list th e appropriate litera
ture reference. T he search procedure has
b een designed in an interactive m ode so
th at even an individual w ho has never
used it may obtain an explanation for a
particular problem , b u t the exp erienced
searcher can by-pass th e longer interac

tive search routine. This m ode of opera


tion is in use only at the N ational Insti
tutes o f H ealth, (NIH ) and a sim pler
procedure is used in E vanston H ospital.
T he m ost im portant use of a com puter
in setting up the CLA U D E (Com puter
L isting o f A bnorm al and U sual D rug E f
fects) concept may be th at of a text editor
and sorter. Scanning a printout is m uch
m ore efficient than searching the file in
the com puter, except for any inform ation
that is not yet available on a printout. It is
our intention to reproduce printouts of

270

FOBMAN AND YOUNG

th e file in a journal w ith a w ide circula


tion to th e appropriate audience w h en a
significant am ount o f new inform ation
has b e en added to th e m aster-file. T he
second edition has recently b een p u b
lish ed .22 It includes som e inform ation on
th e probabilities of certain effects occur
ring, as w ell as an indication of the con
centration of drug at w hich th e effects
occur, at least for the m ethodological
effects.
T he file is used routinely in the
laboratory at N IH in an attem pt to explain
abnorm al te st resu lts. T he re sid e n t
physicians affiliated w ith th e clinical
chem istry service discuss the results w ith
the patient-care physicians to determ ine
if the results w ere due to the patien ts
clinical state or to a drug effect. This
close m onitoring of test results has led to
recognition of deficiencies in w hat is b e
lieved are specific enzym atic procedures
for the m easurem ent of glucose and uric
acid. L ikew ise, th e guaiac procedure for
occult blood in feces was found to yield
false negative results un d er certain cir
cum stances. T his has prom pted the de
velopm ent of a m ore specific procedure
(Jaffe e t al. unpublished).
T he file m ay be q u eried in response to
questions from clinical staff at N IH , to
physicians and to laboratory scientists
throughout the country w ho subm it th eir
problem s by letter or telephone. T he file
has b een u sed to provide inform ation for
a pharm aceutical m anufacturing com
pany preparing a new drug application to
th e F ood and D rug A dm inistration. For
the latter organization, th e file has b een
u sed as a background resource for pro
duct class standards.
O n m any occasions, th e file has pro
vided inform ation about effects of drugs
o f w hich the user was previously una
w are. U ndoubtedly, this has h elped in
the care of som e patients. Several cases
have b een brought to light in w hich pro
longed w orkups o f unusual test values

w ere avoided ow ing to the sim ple expla


nations provided by the file. It is ex
p ected th at the application o f th e file w ill
be expanded by introducing it in a re
vised form into several hospitals for on
line interpretation of data. Also, discus
sions have b e e n h eld w ith several
different institutions overseas to set up
national centers for dissem ination of in
form ation and to provide better m onitoring
of foreign language publications to aug
m ent th e content of the file.
R eferences

1. BORUSHEK, S. and GOLD, J.: Com m only used


m edications that interfere w ith routine endo
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2. C araway , W. T.: Chem ical and diagnostic
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Pathol. 37:445-464, 1962.
3. C arr , M. H. and F rank , H. A.: Calcium
analysis in patients being treated w ith EDTA.
C lin. Chem . .3:20-21, 1957.
4. COHON, M. S.: D rug interactions involving
levodopa. Rev. D rug Interactions 1 :45-62,
1974.
5. C o nn ery , A. H .: Pharm acological im plications
of microsomal enzym e induction. Pharm . Rev.
29:317-366, 1967.
6. D ubois , E. L., T allm an , E., and W onka , R.
A.: C hloroprom azine-induced system ic lupus
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7. E b e r t , R.: Oral anticoagulants and drug in
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1968.
8. ELKINS, M. P. and Kabat , H. F.: D rug induced
modifications of laboratory test values. Amer. J.
H osp. Pharm. 25:484-519, 1968.
9. G l y n n ,K. P., C a r f a r o ,A. F., F o w l e r ,C. W.,
and STEAD, W. W.: False elevations o f serum
glutam ic oxaloacetic transam inase due to
paraam inosalicylic acid. Ann. Intern. M ed.
72:525-527, 1970.
10. L it tl e , D. M. and E s t s t o n e , H. J.: Anaes
thesia and the liver. A naesthesiology 25:815853, 1964.
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values. Med. Clin. N. Amer. 53:211-222, 1969.
12. LuClS, O. J. and Lucis, R.: Oral contraceptives
and endocrine changes. Bull. W HO 46:443450, 1972.
13. Sa b a t h ,L. D., G e r st e i n ,D. A., and F i n l a n d ,
M.: Serum glutamic-oxalacetic transam inase.
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A. L., eds., N ew York, Academic Press, pp.
1-45, 1973.
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phenyram idol and bishydroxycoum arin on th e
m etabolism of tolbutam ide in hum an subjects.
M etabolism 26:1029-1033, 1967.
S p e l l a c y , W. N., B u h l , W. C., S p e l l a c y , C.
E., M o s e s , L. E., and G o l d z i e h e r , J. W.:
G lucose, insulin and grow th horm one studies
in long term uses of oral contraceptives. Amer.
J. O bstet. G ynecol. 206:173-176, 1970.
SUNDERMAN, F. W., J r .: D rug interference in
clinical biochem istry. Crit. Rev. Clin. Lab. Sci.
2:4 2 7 ^4 9 , 1970.
S u n d e r m a n , F. W., Jr.: Effects o f drugs upon
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271

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of various conditions and substances on the re
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B., and P e s t a n e r , L. C.: Effects o f drugs on
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