ISSN:
1573-904X
Keywords:
random-effects statistical model
;
bioavailability trials
;
biological variation
;
intersubject variability
;
intrasubject variability
;
CGS 16617
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The intrasubject and intersubject variabilities for CGS 16617, an angiotensin converting enzyme inhibitor, were evaluated in an open-label, repeat single-dose bioavailability trial. Eight healthy male volunteers each received a 20-mg oral dose of CGS 16617 as an aqueous solution on four separate occasions. Components of variance were evaluated for a mixed-effects statistical model in which subjects were regarded as a random factor. While intersubject variability was statistically significant (P 〈 0.05) for all pharmacokinetic variables measured, AUC, C max, t 1/2, and t max, its contribution to the total observed variability was relatively small for AUC, t 1/2 and t max. The proportion of variation due to intrasubject variability was 70, 19, 61, and 72% for AUC, C max, t 1/2, and t max, respectively. Ramifications of the large intrasubject source component of variability as related to bioavailability trials and biological variation are discussed.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1015954609527
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