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From: Kazimierz H. Kozlowski, Pharm. D.
Laboratory of Pharmacokinetics
The Children's Memorial Health Institute
04-736 Warsaw, Poland
I. Identical drug (and pharmaceutical form) and route of
administration - but different number observed disposition rate constants
I have pharmacokinetic data after ingestion 25-hydroxycholecalciferol
(25OHD3) in children with end-stage renal disease. Disposition rate is
2-exponential in majority patients, but in some patients distribution phase
is not visuable ie. only 1-exponential disposition. My question is
concerned population analysis such data.I have performed analyse according
to 2-compartment model with absorpion phase to all data using NONMEM.
However,other drugs may possess similar problem,comments or suggestion
II.Number of disposition half-life and values of terminal half-life (t1/2,z)
could be change after multiple doseing in the case of intensively distri-
buted drugs: amiodarone, tolrestat (see
For same drugs (aminoglycosides) 1-compartment model is used as
simplification, valid for multiple administration. Terminal half-life
be longer, and distribution phase could be not visible in steady-state.
III.In newborns and small children disposition of ganciclovir after 1-hr
infusion is 1-exponential, but 2-exponential in adults.
The problem is what is consequence in the case omitting distribution phase
(immunoglobulin-G) or real terminal disposition phase (too short sampling
period, amiodarone) for some kind of drugs.
Kazimierz H. Kozlowski
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