DRUG DOSAGES CALCULATION

Dr. MOIN UDDIN

Dept. of Pharmacology
ELM & H, LUCKNOW
Objectives
• Define Dose
• General methods for drug calculation
• Calculation of intravenous fluid
• Paediatric consideration
• Prescribing for older people
• Prescribing in Renal Dysfunction
• Posology - the pharmacological study of drug dosage
The dose of a drug:

• Quantitative amount administered or

• Taken by a patient for the intended medicinal effect

• May be expressed as:

 a single dose: the amount taken at one time
 a daily dose
 a total dose: the amount taken during the time-course of therapy
• The schedule of dosing is referred to as the dosage regimen.
Eg. Tab Augmentin 625 mg TDS for 5 days
The dose of a drug is based on:

Its biochemical and pharmacological activity

 Its physical and chemical properties

 The dosage form used

 The route of administration

 Various patient factors

• Dose of a drug for a particular patient may be determined on the basis of
the:

 Patient's age

 Weight

 Body surface area

 General physical health, liver and kidney function and

 Severity of the illness

General methods for drug calculation
[Link] formula

2. Ratio & proportion

3. Fractional equation

4. Body weight

5. Body surface area

Basic Formula:

DxV =A
H
D- desired dose (drug dose ordered by health care provider)

H- on-hand (stock on hand/on label of container)

V- vehicle ( Q- quantity/drug form in which drug comes)

A- Amount calculated to be given to patient

Examples:

Order: Glimipride 2mg OD. How much tablet will you give?

A= D x V
H
Solution: A= 2mg x 1 tablet
4mg

A = 0.5 i.e. half tablet

Ratio and Proportion

H:V=D:X

Where:

H = drug on hand (available)

V = vehicle/drug form (capsule/tablet/liquid)
D = desired dose (as ordered)
x = unknown amount to give
Example:
• Syp Acetaminophen 180 mg PO tds .How many mL should the patient receive?

Solution:
H:V=D:X

120mg : 5mL = 180mg : X mL

120 = 180
5 X
• X= 7.5 ml
 Fractional Equation
• Same as R & P except it is written as a fraction.

H = D
V X
 Body Weight (BW)

• Allows individualization of the drug dose

• Involves 3 steps:
1. Convert pounds to kg
1 Kg = 2.2 lbs

2. Determine drug dose per BW :

Drug dose x body weight = patient dose per day

3. Follow basic formula, R & P

Example:
• Liposomal Amphotericin-B, 5 mg/kg/day IV, not to exceed 600
mg/day. The adult weighs 132 lb.
• What will be the dose?

Solution:
1. Convert pounds to Kg : 132/2.2 = 60kg

2. mg x kg = patient dose: 5 mg/Kg x 60 Kg = 300 mg/day

3. Answer: Liposomal Amphotericin-B 300 mg/day

 Dose calculation for an Individual

1) On Weight Basis ( Clark’s Formula )

Individual dose = Adult dose × Body Weight (in Kg)

70
2) On Body Surface Area (BSA) basis:

Individual Dose = BSA (in m2) × Adult dose

1.73
3) Mosteller’s Formula :
Calculation of intravenous fluid
• Three different methods:

Method 1- three step

Method 2 – two step

Method 3- one step

Drop factors

• Macro drip – 15/ml

• Micro drip – 60/ml

 Method 1: three step
Step 1
Amount of solution = ml/hr e.g 500 ml NS = 166.66 ml/hr
hrs. to administer 3 hr
Step 2
mL per hr = ml/min e.g 166.6 ml/hr = 2.77 ml/min
60 min 60 min
Step 3
Ml/min X drops/ml = drops/min e.g 2.77ml/min × 15drops/ml=41.6
drops/min( ≈42drops/min)
 Method 2 : two step

Step 1:
Amount of fluid = ml/ hr e.g 500 ml = 166.66 ml/hr
hrs. to administer 3 hrs

step 2:
ml per hr X drops per ml = drops/min e.g 166.66 ml/hr X 15 drops/ml
60 mins 60 mins
= 41.66 drops/min
≈ 42 drops/min
 Method 3: one step

Step: Amount of fluid X drops /ml = drops/ min

Hrs to admin. X min/hr

e.g 500 ml X 15 drops/ml

3 hrs X 60 min/hr

= 41.66 drops/min
≈ 42 drops/min
 Example
• RL 1L for 12 hrs. the drop factor is 15drops/ml. Compute the number of
drops/min.

Solution:
Amount of fluid X drops /ml = drops/ min
Hrs to admin. X min/hr

Drops/min = 1000 X 15 = 20.8 drops/min

12 X 60 ≈ 21 drops/min
Paediatric considerations
• “Children are not small adult”.
• Both the pharmacokinetics and responses to drugs may differ in the young
compared with adults
• also differences between
• neonates- 0–28 days [Early neonate: 0–7 days; Late neonate: 8–28 days]
• infants (29th day–12 months)
• Toddler 1–2 years
• Preschool 2–5 years
• Because many metabolic and physiological processes are immature at birth
and develop rapidly in the first months of life.
Absorption
• Slow rates of gastric emptying and intestinal transit until about 6 months of
age which may slow the rate of drug absorption in neonates & infants.

Distribution
• Blood brain barrier remains immature at birth, so drugs can gain access to the
CNS easily & may cause toxicity.
• Neonates and young children have a lower body fat content and higher total
body water than adults, so water soluble drugs have relatively higher Vd.
• Have a lower plasma albumin & alpha-1 acid glycoprotein concentration, so
drugs which are highly bound to plasma proteins may have high free drug
level. This results in higher distribution & lower peak concn of protein bound
drugs, such as cefazolin.
Metabolism

• Drug-metabolizing enzyme systems are immature in the neonatal liver, and

first-pass metabolism and hepatic drug clearances are low.

• Especially for substrates of CYP1A2, CYP3A4 and glucuronidation

• Chloramphenicol - Grey baby syndrome, is due to poor glucuronidation

reaction occurring in the baby specially in premature.
Renal elimination
• Renal function in the neonate and infant is much less developed than in
children or adults

• GFR of neonate is 30-40% of adult & reaches adult value by 1 year of age.

• Tubular secretion gradually increases to adult value until age of 6-12 months.

• Tubular reabsorption gradually increases & reaches its maturation around 3

years of age.

• Because of low GFR & immature tubular transport, half-life of drugs excreted
by glomerular filtration (gentamicin) & tubular secretion (penicillin) are
prolonged.
1) For children up to 2 years of age

a) Fried’s rule
Paediatric dose = Adult dose X Age in months
150

b) On Weight basis (Clark’s formula)

Paediatric dose = Adult dose X Body Weight(in Kg)
70
2) For Children > 2 years of Age

a) Young’s Formula
Paediatric dose = Adult dose X Age in years

Age in years + 12

b) Dilling’s Formula
Paediatric dose = Adult dose X Age in years

20

c) On Body Surface Area(BSA) basis:

 Geriatric Considerations

• Changes occur in both the pharmacodynamics and pharmacokinetics of drugs

with increasing age.
• Reduction in total body water and non-fat body mass with a relative increase
in body fats.
• S. Albumin concentration is also reduced during aging by 30% in comparison
to younger age.
Example: Phenytoin is highly protein(albumin)-bound drug leading to more
free phenytoin availability due to reduced albumin levels.

• Absorption of levodopa is increased due to a reduced amount of dopa-

decarboxylase in the gastric mucosa.
Metabolism

• Size of the liver and its blood flow decreases.

• Enzyme activity per hepatocyte probably shows , particularly phase 1

metabolic reactions is reduced.

• Because lower hepatic metabolism increases oral bioavailability and reduces

systemic clearance, raising plasma drug concentrations.

• The drug Clearance by the liver depends on the capacity of the liver to extract
the drug from the blood passing through the organ & the amount of hepatic
blood flow.
 Renal elimination
• Creatinine clearance slightly reduce in elderly, due to physiological changes i.e.
reduction in Renal blood flow, decrease in kidney mass & reduction in size and
number of functioning nephrons.

• Clinical importance of such reduction of renal excretion is dependent on the

likely toxicity of the drugs with narrow therapeutic index e.g Aminogylcosides,
digoxin, lithium, warfarin etc.

• Pharmaceutical manufacturers generally use Cockroft-Gault formula while

recommending dosage adjustments for renal excreted drugs.

• Creatinine clearance is used as an estimate of GFR

Pharmacodynamic changes in elderly

• Studies revealed that they are more sensitive to sedative hypnotics & Digoxin.
• Evidence of a greater inhibition of synthesis of Vitamin k-dependent clotting
factors at similar plasma concentration of warfarin in elderly compared with
young patients.
• Reduced response of β-adrenergic receptors to agonists & antagonists due to
reduced synthesis of cyclic-AMP following receptor stimulation.
• Anticholinergic drugs may precipitate urinary retention.
• Because of slow circulation, onset of action slow even with IV drugs e.g IV
General anaesthetics are required in high doses.
Dose calculation in Renal Dysfunction

• Kidney is the main organ of elimination of majority of drugs

• Any Renal disease affecting elimination of excretory products will require

reduction in doses of drugs which is related to creatinine clearance

Creatinine clearance can be calculated by:

 Cockroft Gault’s Formula

a) In Males
b) In Females
a) In Male

Creatinine clearance(ml/min) = [140 - Age in years] X Weight (Kg)

72 X Serum Creatinine (mg/dl)

b) In Female

Creatinine Clearance(ml/min) = 0.85 X Creatinine clearance in Male

Dose adjustment in Renal Dysfunction :

• Loading dose does not changed (except in edema) as it depends upon apparent
volume of distribution.

• Maintenance dose of drugs eliminated through kidney is dependent on

clearance and is-
Maintenance dose = Target Plasma Cocn X Clearance on IV administration

• In Renal dysfunction, Clearance is reduced, hence maintenance dose is also

reduced.
Dose in Renal dysfunction(Drd) = Normal dose X CLrd
CL
CL- Normal Clearance
CLrd- Clearance in Renal dysfunction

Normal Creatinine clearance is 120ml/min & 75% reduction shows renal

dysfunction requiring dose reduction.

Reduced GFR (75% at 50 years & 50% at 75 years) delays excretion of drug and
requires dose reduction.
• Percentage of dose reduction in renal dysfunction=Percentage of Creatinine
Clearance reduction.
Example :
1) Calculate Creatinine clearance in a 70 year old male weighs 70 kg. S.
creatinine is 0.8 mg/dl.

Solution:
Creatinine clearance(ml/min) = [140 - Age in years] X Weight (Kg)
72 X Serum Creatinine (mg/dl)
= [140-70] X 70
72 X 0.8
= 85.06 ≈ 85 ml/min
2) Calculate Creatinine Clearance in the same individual in renal dysfunction
when [Link] is 3 mg/dl and calculate the dose of Ciprofloxacin in Renal
dysfunction.[ Normal dose of Ciprofloxacin 500 mg BD]

Solution:
Creatinine clearance(ml/min) = [140 - Age in years] X Weight (Kg)
72 X Serum Creatinine (mg/dl)
= [140-70] X 70
72 X 3
= 22.68 ≈ 23 ml/min
• Dose in Renal dysfunction(Drd) = Normal dose X CLrd
CL
= 500 mg X 23
85
= 135.2 ≈ 135 mg
General Precautions in Renal Dysfunction

• Drugs excreted unchanged like atenolol, aminoglycosides, digoxin,

phenobarbitone, etc. should be avoided.

• Nephrotoxic drugs e.g aminoglycosides, potassium sparing diuretics (cause

hyperkalaemia & cardiac depression), pethidine, tetracyclines (except
doxycycline & tigecycline), nitrofurantoin, amphotericin-B, cisplatin,
cyclosporine, Vancomycin, sulphonamides, heavy metals etc. should be
avoided.

• In renal failure, furosemide is preferred over thiazides, as thiazides decreases

GFR.
• Drugs like uricosurics, Cholecalciferol, are ineffective & should be avoided while
in anemia due to chronic renal failure, hematinic are to be used with
Erythropoietin.

• Poor excretion of urinary antiseptics may lead to systemic toxicity, hence

should be avoided.

• Therapeutic drug monitoring is to be done whenever necessary.

Thank you