The pharmacokinetics of low-dose thalidomide in Japanese patients with refractory multiple myeloma.
Thalidomide has been used for the treatment of refractory multiple myeloma, the dosage in Japan is lower than in other countries; however, there is little information on the pharmacokinetics and their relationship with the drug response. The aim of this study was to characterize the pharmacokinetics of low-dose thalidomide in Japanese patients with refractory multiple myeloma, and to examine the relationship between pharmacokinetics and adverse events. On the first and second days, a 100 mg capsule was administered to 8 Japanese patients after breakfast and blood samples were obtained. The plasma concentrations were measured using HPLC and analyzed based on a one-compartment model. If intolerable adverse events were not observed for 14 d, the dose was increased to 200 mg. The average apparent volume of distribution (Vd/F), apparent total clearance (CL/F) and area under the plasma concentration-time curve from 0 to infinity (AUC0-infinity), which were 45.3 l, 5.5 l/h and 21.7 microg.h/ml, respectively, with smaller Vd/F and CL/F and larger AUC0-infinity than in Caucasian populations. This pharmacokinetic difference may explain the dose difference between Japan and other countries. Adverse events were associated with AUC0-infinity, which was best correlated with plasma concentration at 12 h after administration. The 12-h time point was suggested to be a capable indicator for "safety-oriented" therapeutic drug monitoring of thalidomide.
Kamikawa
Rintaro
R
Department of Pharmacy, Hiroshima Red Cross Hospital, and Department of Clinical Pharmacotherapy, Hiroshima University, Japan.
Ikawa
Kazuro
K
Morikawa
Norifumi
N
Asaoku
Hideki
H
Iwato
Koji
K
Sasaki
Ayako
A
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D044466:Asian People; D002214:Capsules; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D007564:Japan; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000208:ethnology / Q000378:metabolism*; D013792:Thalidomide / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D014018:Tissue Distribution; D016896:Treatment Outcome
D002214:Capsules; D007166:Immunosuppressive Agents; D013792:Thalidomide