Comparison of Linezolid Pharmacokinetics from Phase I Studies of Japanese and Caucasians

Authors: Cirincione B, Chiba K, Stalker D, Sokolowski M, Grasela TH, Antal E, Bruss J
Conference: ASCPT
Keywords: anti-infectives, Asia, bridging analysis, ethnic differences, infectious disease, Japan, non compartmental, noncompartmental, PK, Shapiro-Wilk statistic, Wilcox rank-sum
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Abstract

Purpose. This bridging analysis compared pharmacokinetic (PK) parameters for linezolid (lzd) observed in Japanese (J) and Caucasians (C) in traditional PK Phase I studies.

Methods. PK data were pooled from 5 studies of lzd administered to healthy males as 125-625mg multiple (BID) IV or oral doses. Non compartmental methods were used to estimate PK parameters.

Results. PK parameters were pooled from 93 males (57% J) with a mean (SD) age of 24.3 (6.0) years and a mean (SD) weight of 69.0 (10.8) kg. Only CL for C at the 125mg dose level showed large variability. For all other doses the estimated CL values remained in a narrow range in both groups. The range of J CL values was within the range of values for C, while mean (SD) CL for J (dose 250-625mg BID) was lower than that of C (70.44 (16.60) vs. 105.47 (37.81) mL/min). The mean weight-corrected CL estimates were 1.14 (0.27) and 1.38 (0.52) mL/min/kg for the J and C subjects, a difference of 20% that was deemed not to be clinically significant. For distribution volume, differences between the groups were eliminated by correcting for body weight.

Conclusions. Overall, minimal differences in PK were noted. Based in part on this information, lzd was approved for use in Japan/Asia at the same dosage used in the U.S.

American Society for Clinical Pharmacology and Therapeutics (ASCPT); Atlanta, Georgia; March 2002

By B. Cirincione, K. Chiba, D. Stalker, M. Sokolowski, T. Grasela, E. Antal, J. Bruss