title: Intra- and intersubject variability: mixed-effects statistical analysis of repeated doses of an angiotensin converting enzyme inhibitor, CGS 16617.
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 less than 0.05) for all pharmacokinetic variables measured, AUC, Cmax, t1/2, and tmax, its contribution to the total observed variability was relatively small for AUC, t1/2, and tmax. The proportion of variation due to intrasubject variability was 70, 19, 61, and 72% for AUC, Cmax, t1/2, and tmax, respectively. Ramifications of the large intrasubject source component of variability as related to bioavailability trials and biological variation are discussed.
authors.affiliation: Clinical Pharmacokinetics Section, Pharmaceuticals Division, CIBA-GEIGY, New York 10502.
authors.forename: G M
authors.initials: GM
authors.lastname: Kochak
authors.forename: R A
authors.initials: RA
authors.lastname: Smith
authors.forename: R L
authors.initials: RL
authors.lastname: Choi
authors.forename: V
authors.initials: V
authors.lastname: John
authors.forename: V
authors.initials: V
authors.lastname: Tipnis
authors.forename: F
authors.initials: F
authors.lastname: Honc
authors.forename: J K
authors.initials: JK
authors.lastname: deSilva
authors.forename: D J
authors.initials: DJ
authors.lastname: Weidler
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics*; D001552:Benzazepines / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D008954:Models, Biological; D013223:Statistics as Topic
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; C052134:libenzapril