Exploratory analysis of population pharmacokinetic data from clinical trials with application to isradipine.
Drug level monitoring during routine clinical visits in the course of phase III trials provides a means to document pharmacokinetic variability in a patient population. Such a pharmacokinetic screen was performed for the new calcium antagonist isradipine. A total of 697 blood samples were collected at any time after the morning dose from 252 patients who had received oral doses of isradipine. Three approaches of data analysis based on exploratory (graphical and statistical) techniques were used to relate plasma level to patient demographic data and laboratory parameters. The pharamacokinetics of isradipine seemed to be influenced by the demographic variables of age (already detected in conventional studies) and weight, as well as by the blood serum levels of inorganic phosphorous, uric acid, alkaline phosphatase, and bilirubin, but only to a small, clinically irrelevant extent. The findings from the three approaches were complementary. They suggest that a pharmacokinetic screening in clinical trials is feasible at reasonable experimental cost and effort and provides useful data on interindividual and intraindividual pharmacokinetic variability in patients.
Laplanche
R
R
Drug Safety Assessment Division, Sandoz Pharma, Basel, Switzerland.
Fertil
B
B
Nüesch
E
E
Jais
J P
JP
Niederberger
W
W
Steimer
J L
JL
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D000704:Analysis of Variance; D001682:Biological Availability; D001827:Body Height; D001835:Body Weight; D002121:Calcium Channel Blockers / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D017275:Isradipine; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics*; D012737:Sex Factors
D002121:Calcium Channel Blockers; D011725:Pyridines; D017275:Isradipine