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[object Object]
 The major causes of inter subject pharmacokinetic  variability are  :- 	,[object Object]
Age          1.Drug metabolism in new born        2.Plasma protein bonding in new born        3.Renal excretion in new born        4.Drug metabolism in children ,[object Object]
Disease,[object Object]
[object Object]
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)               Children (4 to 9 years)                Adults (16 to 37 years)                Elderly subjects (more than 70 years)
[object Object]
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.
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. ,[object Object]
Very elderly patients 75 to 92 years of age had an average clearance of about 8 ml/min.,[object Object]
Most of the enzymatic microsomal systems required for drug metabolism are present at birth, but their  concentration are usually lower than adult levels.
In  general drugs subject to  biotransformation are eliminated more slowly in newborn than in adult.,[object Object]
Sulfate conjugation seems to be as efficient in newborns as in adults, but conjugation with glucuronic acid is considerably reduced, reaching adult level only after 3 years of age.
This deficiency is responsible for the serious adverse effects observed in newborn after administration of chloramphenicol a drug that is ordinarily conjugated with glucuroni acid.  ,[object Object]
The amount of unchanged theophylline in urine in premature infants decreases with postnatal age, whereas the excretion of metabolites increases with age. ,[object Object]
In each case binding in plasma protein is level in the newborns than in the adults.
Increase in plasma protein binding is an increase in apparent volume of distribution in the newborn.

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Pharmacokinetic variability

  • 1.
  • 2.
  • 3.
  • 4.
  • 5.
  • 6.
  • 7. Drug binding, metabolism, and excretion may change as a function of age.
  • 8. The study panel was divided into 5 groups: Newborns (2 to 3 days) Infants (1 to 12 months) Children (4 to 9 years) Adults (16 to 37 years) Elderly subjects (more than 70 years)
  • 9.
  • 10. 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.
  • 11. 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.
  • 12.
  • 13.
  • 14. Most of the enzymatic microsomal systems required for drug metabolism are present at birth, but their concentration are usually lower than adult levels.
  • 15.
  • 16. Sulfate conjugation seems to be as efficient in newborns as in adults, but conjugation with glucuronic acid is considerably reduced, reaching adult level only after 3 years of age.
  • 17.
  • 18.
  • 19. In each case binding in plasma protein is level in the newborns than in the adults.
  • 20. Increase in plasma protein binding is an increase in apparent volume of distribution in the newborn.
  • 21.
  • 22.
  • 23. The difference process of renal excretion on mature at different rates,
  • 24. Average glomerular filtration rate is 38.5 ml/min.
  • 25.
  • 26.
  • 27. Older infants age (6 months to 12 years) has higher drug metabolism capacity rates compared to adults. for example, clindamycin theophylline valproic acid Has faster elimination rate.
  • 28.
  • 29. Formula used to determine dosage form
  • 30. Child dose= SA of child(m²) ------------------------------
  • 31.
  • 32. 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.
  • 33.