7 - Environmental Variability

Question 1

Most important determinant determinant of drug dose

Answer 1

• Body size, renal function , PMA
• large differences in loading doses, not as large differences in maintenance doses - due to weight and clearance relationship (non-linear)
• fat mfree mass and fat mass
• renal function (10 fold differnece in clearnace - GFR rate) - use serum creatinine to calculate GFR
• Hepatic function - measure liver damage, however sometimes no change in hepatic clearance

Question 2

Maturation and ageing

Answer 2

• Full term delivery (PMA) is 30% adult drug clearance
• Premature neonates - far less
• age accounts for a 10 fold increase in GFR from 24 weeks PMA to 1 year
• ageing - minor influence once adjusted for other factors

Question 3

Clearance maturation

Answer 3

Post menstrual age determines clearance maturation until age of 2, then weight does

• clearance increases with weight and age
• allometric size predicts increasing clearance per kg with lower weights
• below 2 years, age immaturity of drug clearance

Question 4

Why is dose per kg of weight higher at 2 years?

Answer 4

• 2 year old children need a higher dose per kg of body weight
• Below 2 eyras of age immaturity of drug cleraance has a major effect on clearance so clearance per kg decreases
• the leads to a peak in clearance at 2 yeras
• maintenance doses are commonly expressed per kg in clinical practice -

basically cleranace per kg of weight is increased at 2 years so need a greater miantenance dose at this age per kg of body weight