This document discusses sources of pharmacokinetic variability between individuals. Body weight, age, sex, and pregnancy can impact how the body handles and eliminates drugs. Larger body weight is associated with higher volume of distribution and lower plasma drug concentrations of some medications. Drug clearance typically increases with age from infancy through adulthood and then decreases in elderly patients. Some drugs are cleared more rapidly in males compared to females. During pregnancy, changes in gastric emptying, plasma volume, protein binding and renal blood flow can influence drug absorption, distribution and elimination. Consideration of these factors is important for optimizing drug dosing for each individual patient.

1. TOPIC : PHARMACOKINETIC VARIABILITY
Prepared By :
Sandeep Kumar

2. CONTENT
 INTRODUCTION
 BODY WEIGHT
 AGE
 SEX
 REFERENCE

3. INTRODUCTION
 "Inter-individual variations of a drugs
pharmacokinetic parameters, resulting in fairly
different plasma concentration-time profiles
after administration of the same dose to
different patients."
 when individual are given identical dose of a
drug large difference in pharmacological
response may be see.

4. Eg: 17 Patients
Sedative dose (Midazolam)
i.v. continuous dose
Half life of midazolam
1Patient less than 2hr
10Patients less than 4-6hr
6Patients less than 10hr

5. Eg: 72 rats after interperitoneal administration
of Pentobarbital sodium (30mg/kg) varied
sleeping time range 30-190min. Paralysis in
96 rats after interperitaoneal administered of
zoxazolamine (110mg/kg) varied from
100-850.

6. BODY WEIGHT
Administration of the same dose of the drug to
patient with different body weight may produce
different drug plasma concentration.
IBW(MAN)= 50kg 1kg/2.5cm above or below
150cm in height.
IBW(WOMAN)= 45kg 1kg/2.5cm above or
below 150cm in height.

7. Eg: Patent weight 150 kg is predicted to have an
apparent Vd of 26.1 L & normal weight
Patient will be Vd 18.2 L Amikacin drug.
40% higher normal Person than high weight.
Some drug: Ceffein , Lidocaine Lorazepam
Theophylline.
fat person slime person
Vd ↑es Vd ↓es
plasma cons↓es cons.↑es
( same dose 100mg )

8. AGE
 Age itself, rather than body size and composition,
also affects the distribution and elimination of
many drugs.
 Drug binding, metabolism, and excretion may
change as a function of age.
 The study panel was divided into 5 groups:
Newborns (2 to 3 days)
Infants (1 to 12 months)

9. Children (4 to 9 years)
Adults (16 to 37 years)
Elderly subjects (more than 70 years)
 Comprehensive examination of the effect of age on
drug elimination has been reported for ceftriaxone.
 Clearance increased from 0.9 to 2.5 ml/min. when
comparing patient 1 to 8 days old with patient 9 to
30 days old.

10.  The mean clearance of ceftriaxone in children
ranging in age from 1 to 12 months and from 1 to
6 years was 6.2 ml/min. and 9.1 ml/min.
respectively.
 The 18 to 49 years old age group had the highest
clearance of ceftriaxone, 17 ml/min.
 Older groups of patient had progressively lower
value of clearance.

11.  Very elderly patients 75 to 92 years of age had an
average clearance of about 8 ml/min
 Some drugs
• clindamycin
• Theophylline
• Valporic acid
Child dose = Adult dose (mg/day)

12.  comparative study of procainamide in children's
and adults
Parameter Children Adults
Half life 1.7 hr 2.5 –5 hr
plasma clearance 20ml/min/kg 9 ml/min/kg

13. SEX
 Sex related difference in the capacity of rates to
metabolize drugs are widely recognized.
 The clearance of Phenprocoumon was significantly
lower in female than male.
 Vd smaller female than male.
Eg: Tamazepam, Oxazepam, Lorazepam
 The clearance of Acetaminophen was 40%
greater in males than females

14. PREGNANCY
 Pregnancy is a condition associated with
physiological changes that can affect the
absorption, distribution and elimination of drugs.
 The increase in gastric ph, the decrease in gastric
emptying rate and the slower motility associated
with pregnancy can affect the rate and extent of
drug absorption.

15.  The significant increase in plasma volume during
pregnancy can increase the drug volume of
distribution and the decrease in albumin serum
concentration can decrease the protein binding of
drugs.
 The increase in cardiac output in general and the
renal blood flow in particular during pregnancy
increase the renal elimination rate of drugs such
as ampicilline, digoxin, and lithium.

16. REFERENCE
 Biopharmaceutcs and Pharmacokinetics
Gibaldi page no. 234-254.
 www.authorstream.com

17. THANK YOU…