Comparison of Laboratory Safety Data from Japanese and Non-Japanese in Linezolid Phase I Studies

Authors: Cirincione B, Lobek F, Chiba K, Stalker D, Sokolowski M, Grasela TH, Antal E, Bruss J
Conference: ASCPT
Keywords: absolute neutrophil, alanine transaminase, ALT, ANC, anti-infectives, Asia, aspartate transaminase, AST, ethnic, hematologic, hemoglobin, hepatic toxicity, infectious disease, Japan, Linezolid, platelet, RBC, red blood cell, WBC, white blood cell
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Abstract

Introduction. The laboratory safety data of linezolid (lzd) pooled from 6 multi-dose Phase I studies were compared in 65 Japanese (J) and 56 non-Japanese (non-J) subjects.

Methods. Hematologic parameters assessed for toxicity were hemoglobin (HGB), red blood cell (RBC), white blood cell (WBC), platelet (plt) and absolute neutrophil counts (ANC). Hepatic toxicity was assessed by alanine and aspartate amino transferases (ALT/AST) concentrations. Scatterplots of the absolute value of the safety parameter and the end of treatment (EOT) change from baseline versus the exposure measure (cumulative dose) were examined.

Results. No relationship was apparent between exposure and absolute value or EOT change from baseline for the HGB, RBC, ANC, ALT, or AST. Trends for mild decreases in plt values with increasing exposure were apparent in both populations. For WBCs, the J subjects appeared to have lower baseline values, but had response trends similar to non-J over time.

Conclusions. Overall, there were no relevant differences in hematologic or hepatic response to similar lzd exposure between J and non-J subjects. 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, F. Lobek, K. Chiba, D. Stalker, M. Sokolowski, T. Grasela, E. Antal, J. Bruss