random-effects statistical model
Springer Online Journal Archives 1860-2000
Chemistry and Pharmacology
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.
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