A comprehensive review of the pharmacokinetics of approved therapeutic monoclonal antibodies in Japan: Are Japanese phase I studies still needed?
Ethnic evaluation of the pharmacokinetics and safety of new drugs is required in Japan before implementing bridging or joining global studies. As therapeutic monoclonal antibodies (mAbs) show limited ethnic differences, their pharmacokinetics and safety in Japanese individuals could be estimated from prior non-Japanese studies. Therefore, there is potential to re-evaluate the development program for mAbs in Japan. We reviewed the pharmacokinetics of mAbs approved in Japan. Although some differences had been observed in pharmacokinetics of mAbs between Japanese and non-Japanese populations (mainly Caucasians), these differences were attributed to differences of body weight and/or antigen levels. Moreover, the influential factors can be estimated without conducting regional pharmacokinetic/safety studies. The pharmacokinetics of some mAbs is presumably non-linear and show differences between healthy volunteers and patients because of differences in antigen levels. However, for 10/24 mAbs approved in Japan, Japanese healthy volunteer studies were conducted before the patient studies. Additionally, for the mAbs that showed ethnic differences in pharmacokinetics, the doses selected in subsequent patient studies were the same as the doses approved in the United States. In this review, we discuss new drug development strategies in various regions, and assess the need for regional pharmacokinetics/safety studies before joining global studies.
Laboratory of Clinical Pharmacology, Yokohama College of Pharmacy, Yokohama, Japan.|Department of Drug Development and Regulatory Science, Keio University Graduate School of Pharmaceutical Science, Tokyo, Japan.
Koji
K
Chiba
Discovery Medicine & Clinical Pharmacology, Research & Development, Bristol-Myers Squibb, Princeton, NJ, USA.
Hiroyuki
H
Yoshitsugu
Department of Drug Development and Regulatory Science, Keio University Graduate School of Pharmaceutical Science, Tokyo, Japan.
Yuto
Y
Kyosaka
Clinical Research Planning Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
Satofumi
S
Iida
Clinical Research Planning Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
Koichiro
K
Yoneyama
Clinical Sciences, Bayer Pharma AG, Berlin, Germany.
Takahiko
T
Tanigawa
Department of Drug Development and Regulatory Science, Keio University Graduate School of Pharmaceutical Science, Tokyo, Japan.
Takashi
T
Fukushima
DMCP, Clinical Research, Bristol-Myers K.K., Tokyo, Japan.
Masaki
M
Hiraoka
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics*; D017321:Clinical Trials, Phase I as Topic; D017277:Drug Approval; D005006:Ethnicity; D006801:Humans; D007564:Japan
D000911:Antibodies, Monoclonal
Japan; monoclonal antibody preparations; regulatory affairs