Lecture 8: Variability due to env Flashcards
most important quantitive determinant of drug dose
weight - has a massive range
allometric scaling?
used because the mass overhead from delivery and support systems increases total body mass without a linear increase in function.
CLchild = CLadult x (weightc/weighta)3/4
The allometric exponent of 3/4 describes this non-linear relationship for clearance
The linear relationship between mass and structural properties such as volume of distribution uses the exponent 1
Body composition approaches
- look at fat free mass vs fat mass
- fat mass around 22% in men and 28% in women
- drug clearance is driven mostly by fat free mass but also by the fat mass. The fraction of fat mass predicting drug elimination and distribution varies from drug to drug
Other determining factors of drug clearance?
- renal function (10fold)
- hepatic function
- age of baby
- maturation and ageing
Renal function?
glomerular filtration is = 7L/h
even in terminal renal failure it is about 0.5L/h due to some non-renal clearance that adds to the 0.5L/h in the failing kidney
Prediction of renal function?
We use serum creatinine to calculate clearance (CLcr)
Creatinin compared (as a % of) to average for their weight and age
Hepatic function differences?
There is variability but NO predictable difference
LFTs measure damage not the function
Ways of measuring a babys age?
Maturation and ageing of kidnt and liver?
PNA - Post natal age (doesn’t account for in utero maturation)
PMA - post mestrual age (on av. 2 weeks older than actual age)
PCA - Post conception age (not widely recorded as hard to know)
At full term is about 30% and takes about 2 years for full maturation
CL and age?
CL may decrease slightly with age, however when compared to other factors in play it is nothing
CL in /kg variation?
Past 2 years weight is the biggest predicting factor for clearance BUT at 2 years of age the CL /kg is at its highest
Rules for baby dosing?
PNA and PMA and weight are added together to estimate % of adult dose.
