Details

Autor(en) / Beteiligte

• KOCHAK, G. M
• SMITH, R. A
• CHOI, R. L
• JOHN, V
• TIPNIS, V
• HONC, F
• DESILVA, J. K
• WEIDLER, D. J

Titel

Intra- and intersubject variability: mixed-effects statistical analysis of repeated doses of an angiotensin converting enzyme inhibitor, CGS 16617

Ist Teil von

• Pharmaceutical research, 1989-04, Vol.6 (4), p.328-331

Ort / Verlag

New York, NY: Springer

Erscheinungsjahr

1989

Quelle

SpringerLINK Contemporary (Konsortium Baden-Württemberg)

Beschreibungen/Notizen

• 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.