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By. LUKMAN ARIFIN, dr.,AFK

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Dose is a number of ingredient in a given unit
administered within a certain period. It is used
for determining the number of drugs/toxic
materials, chemicals, bacterial toxin / antitoxin,
serum and vaccines that are applied or enter
into human body or animal in treatment or
experiment to give rise symptoms or not in the
human body or the animal.
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THE MEASURE OF DOSE ON THE
PRESCRIPTION
a. Weight Units : mcg-mg-g-kg
b. Volume units : l-ml-l
Small spoontful = 5 ml
Large spoonful = 15 ml
Cth = Teaspoonful = 5 ml
C. = Tablespoonful = 15 ml
Guttae (drips) = International standard of drop is one gram destilated water
(I ml) = 20 drop at temperature 20
O
C
c. International units = (I.U)
Nystatin 500.000. I.U
Vitamin A 20.000. I.U
d. PRECENTAGE
% b/b Weight per weight
% b/v weight per volume
% v/v volume per volume
% v/b volume per weight
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TERMINOLOGY OF DOSES
MINIMAL (MINIMUM DOSE) the smallest Quantity of an agent that is likely to
produce an appreciable effect

EFFECTIVE DOSE the quantity of an agent which will produce the effect for
which it is administered

OPTIMUM DOSE the quantity of an agent which will produce the effect desert
without unfavorable side effects.

DOSIS CURATIVEVA the minimum amount of a therapeutic agent that will
effect a cure

DOSIS TOLERATA the largest amount of a therapeutic agent that can be given
with safety

TOXIC DOSE the amount of an therapeutic agent which will cause toxic
symptoms.

LETHAL DOSE the amount of agent which will cause death
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USUAL DOSE :
AVERAGE DOSE :
DAILY DOSE :
DIVIDED DOSE :
SINGLE DOSE :

LEVEL OF THERAPEUTIC DOSE

1. INITIAL DOSE
2. ADJUSMENT DOSE
3. MAINTENANCE DOSE
4. MAXIMUM DOSE
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1. AGE, BODY WEIGHT
2. SEX
3. ROUTE OF ADMINISTRATION
4. ABSORPTION AND EXCRETION
5. DISEASE
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LITERATURE OF DOSAGE GUIDELINES
1. FORMAL SOURCES
TEXT BOOKS + REFERENCE BOOKS : Pharmacology, pharmacy
REFERENCE BOOKS published by Health Dept :
- Indonesia pharmacopea, National
- FORMULARIUM
- Indonesia Extra Pharmacopea

2. OTHER SOURCES :
IIMS - MIMS INDONESIA
MEDICAL - PHARMACEUTICAL MAGAZINES.
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No. Indication ADM Usual Dose Max. Dose

each daily each daily

1. Acetamonophenum Analgetic Oral 500mg 500-2g
Antipyretic

2. Metampyronum Analgetic Oral 500mg 1.2g

3. Atropinisulfas Parasympatholytics Oral 0.25mg 1-2g 2 mg 4 mg
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CALCULATION OF MAXIMUM DOSE
R/ Atropinisulfat 1.5 mg
Saccharum lactis qs
m.f. pulv dtd no x
4 dd.pulv.I

Single maximum dose : 2 mg
Daily maximum dose : 4 mg

CALCULATION :
Single M.D = 1.5/2 x 100% = 75%
Daily M.D. = 4x 1.5/4 x 100% = 150%
MG will surpass when more than 100%
Single MD 75% ; MD will not surpass
Daily MD 150% ; Daily MD will surpass

Attention that :
* At the end of drug statement, brief signature or exclamation sign (!) should be started the
drug can be done
* No brief signature or! the drug can not be done ask again the presciriber
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DOSE CALCULATION
R/ sol,.Charcot 200mg
Adde
Luminal Na 500 mg
Pyramidone 1500 mg
Largactil 1200 mg
M.D. 2 dd C

LUMINAL
Single MD 250 mg
Daily MD 500 mg
Maximum Dose for single use :
15 (1 C = 15 g)
x 500 mg = 40 mg
203.2 (the number of Liquid and drug)

The proportion = 40/250x 100% = 16%
The Daily Maximum Dose = 2 x 40 mg = 80 mg
The proportion = 80/500 x 100% = 16%
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Single MD 1 g
DAILY MD 3 g
Maximum Dose for Single use :
15
x 500 mg = 115 mg
203.2 (the number of Liquid and drug)

The proportion = 115/1000x 100% = 11.5%
The Daily Maximum Dose = 2 x 115 mg = 230 mg
The proportion = 230/3000 x 100% = 77.6%
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The active ingredients are generally similar to those for adult
In contrast, the difference is about the dose variety

Pediatric dosage can be divided into 3 age groups :
1. Neonatus 0 -4 weeks
2. Infant 5 - 52 weeks
3. Childrent 1 - 15 years
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PHARMACOLOGICAL EFFECT OF DRUGS IN
DIFFERENT CHILD AGES

The different perceptions of gastrointestinal tract to drugs occur between
neonatal and infant periods
No significant difference between healthy children and adults
The first week of neonatus : irregular peristaltics
6 - 12 months : delayed gastric emptying
0 - 3 years : fluctuative gastric pH
The intramuscular administration : irregularly reduced
Percutaneous administration : needs larger amount but more rapidly

DISTRIBUTION
The percentage of total body fluid to the extracellular fluid is higher in neonatus
and lesser to equal in the infant age of 12 months than in the adult.
Subcutaneous tissues is the most in age 9 months, lesser in 6 years, but
increased in adolescence.
These affect on weak-soluble drug distribution.
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The plasma protein bounds are lesser in neonatus and
reaches the adult level atage of 10-12 months.

In hyperbilirubinemic neonatus, the drugs that have high
affinity to bind plasma protein, such as sulfonamide,
salicilate and phenytoin, can out the bilirubin toxic to
brain tissue
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Drug metabolism in infant is lower than that in adult

The drugs whose elimination depend on liver, their half-life
time in plasma are longer, for example diazepam, digoxin,
indometacin, acetaminophen, phenobarbitol, salicylate,
chloramphenicol, etc.

The rapid ones : theophyline, anticonvulsant.
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The renal excretion function in neonatus and infant are still minimal
that later will reach the adult level at ages of 6 - 12 months.
Drugs whose their elimination depend on kidney function will be
excreted gradually and consequently have prolonged half-life time.

SENSITIVITY
The more sensitive drugs are narcotics and strong laxantives,
atropine, and sulfas.
On the other hand, more resistant against Phenobarbital, chloral
hydrate, and digoxin.
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THE PEDIATRIC DOSES BY AGE
Formula
YOUNG : < 8 years

n (year)
x adults dose
n-12
DILLING : > 8 years

n (year)
x adults dose
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FREID :

m (month)
x adults dose
150
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CLARK :

W (kg)
-------------- x adult dose
68
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BODY WEIGHT AND PERCENTAGE
The estimated pediatric doses against adult dose based on body weight

AGE BODY WEIGHT (Kg) PEDIATRIC/ADULT DOSE
RATIO (%)

PREMATURE INFANT 1.13 2.5 5
1.81 4 8
2.27 5 10
NEWBORN INFANTS 2.27 12.5
2 MONTHS 4.54 15
4 MONTHS 6.35 20
12 MONTHS 9.98 20
3 YEARS 14.97 33
7 YEARS 22.68 50
10 YEARS 29.94 60
12 YEARS 35.52 75
14 YEARS 45.36 80
16 YEARS 54.43 90
The doses are used in the first 2-3 weeks or when appeared jaundice
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The other calculation is that the
drugs dose is determined by a
given mg for each mg / body
weight kg / times / day body
weight per each or per day
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BODY SURFACE AREA
This is the most appropriate calculation though there are some
arguments because the body surface area do not related directly
to physiologic and metabolic function. However, the application of
the formula is impractical

Formula :
[1.5 x Weight (kg)] + 10 x adults dose (in %)
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Using Normogram
Body Weight Age Surface Area Dose Percentage

3 Newborn 0.2 12
6 3 months 0.3 18
10 1 year 0.45 28
20 5.5 years 0.8 48
30 9 years 1.0 60
40 12 years 1.3 78
50 14 years 1.5 90
65 Adult 1.7 102
70 Adult 1.76 103

Table of Precentile Danekams (very satisfactory)
The Scale of Oediatric Doses
Notes : C = Adult dose n% (based on body surface area)
This scale can be used in 2 ways :
1. Based on Age : read from Ato C, 2. Based on Body Weight : read from B to C (quick)
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When the percentage of the child is less / abnormal, use the
average dose from thescale B to C (based on body weight) and D to
C (based on height)
(12n + 13)
Da = ------------------ Dd (n.g) n = BSA/m2
100

Calculation based on Formula AUGSBERGER (more accurate, derived from
body surface area) :
2 - 12 months (m + 13) % of d.d
1 - 11 Years (4n + 20) % of d.d
12 - 16 years (5n + 10) of d.d

1.5 W + 10
Da = ---------------- Dd (mg) : W = BW/kg
100
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DOSE CALCULATION
1. The adult dose of drug A is 5g. How much is the pediatric
dose for infant at 3 years ?

YOUNG :
3 (years)
Pediatric dose : ------------------------ x 10 mg = 1 g
3 + 12

2. Determine the pediatric dose having 20kg body weight, whereas the adult
dose is 10 mg in average.

CLARK :
20 kg
Pediatric dose ------------ x 10 mg = 2.91 mg
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If the adult dose of drug B is 50 mg, how much is
the pediatric dose for an infant with 0.57 m2 of
body surface area ?
0.57
Pediatric dose ------------------- x 50 mg = 16.5mg
68

If dose of drug C is 0.5 mg/kg/BW/24 hours, how many gram is it
required per week or per 24 hours for a children with 15 kg of body
weight ?

0.5 mg/kg/24 hrs x 15 = 7.5 mg/24 hrs or 0.0075 g/24 hrs
0.0075 g/24 hrs x 7 days = 0.052 g/week
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A drug preparation containing 10 mg/m antibiotics pro
injection. How much is the pediatric dose required for a
child with 8 kg of body weight ? The dose is considered
1.4 mg/mg/kgBW
1.4 mg/kg x 8 kg = 11.2 mg is required 10 mg : 1 ml = 11.2 : Y ml
Y = 1.12 mg as the pediatric dose needed

One mg antibiotics B contains 250 units, then how many units
is the content in 15 mg ?
25 unit/mg x 15 = 3750 units.
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Ages are 64 years or more
The factors occur in elderly :




The drugs via oral have not much changed
Absorption is slow and reduced in the following diseases :
Congestive heart failure
Malabsorption
Iron enteropathy
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Albumin / albumin (?) ration is changed :
At age of 23 years : 1.32
At age of 79 years : 0.87




Liver weight :
40 years 1930 g
90 years 1000 g
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In the general liver function is good, except the
hepatic microsome enzyme cythochrom P450
reduced.
The hepatic Pathway of drug :
In the "Hepatic First Pass Clearance", drug will be metabolized
partially
The drug with high Hepatic Extraction Ratio (HER) such as
Propanolol-lignocaine --> minor systemic circulation, thus the different
route will require different doses too
Intravenous Propanolol : 5 - 10 mg
Propanolol per oral : 80 - 90 mg
First pass effect (FPE) --> low bioavailability of drug up to 4 times

The drugs having FPE : linoxin, chlorpromazine, beta blocker
reserpine, morphine, acetosal, paracetamol, phenylbutazone

HYPERSENSITIVITY
The elderly people tend to expose to the excessive drug effect
"Tissue Sensitivity"
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After 40 years old, the glomerular and tubular filtration rate reduces
1% annually.
In Some diseases, renal blood flow also reduces
The renal function of 70-year people is half than that of 25 year
people
The renal mass generally reduced as many as 30%. The loss of entire
nephrone units indicates the lowering of GFR :
1. 20 - 90 years old : 123 MVL 65 Mol/ml. 1.73 mg
2. 25 - 80 years old : tubular filtration reduced 40%
3. 30 - 90 years old : creatinine excretion decreases from 24
to 12 mg/kg/24 hrs
As the cause of lowering renal function, some drugs show heightening
in their blood levels --> prolonged t 1/2, example : benzylpenicilline,
tetracylline, etc
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Based on renal condition :
1. The drug metabolism factor via kidney
2. Retaining factor of drugs toxic
3. Safety Margin of drugs
In non-toxic active drug, eventhough glomerular rate reduces, the
dose should not be altered : walfarin, tolbutam
The drugs having wide safety margin, such as ampicillin, will not
appear toxic though the creatinine clearance lesser than 2 mol/min
Whereas aminoglycoside group will result in autotoxic when it
increase slightly from the standardized dose.
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