The Pharmacokinetics of Low-Dose Thalidomide in Japanese Patients with Refractory Multiple Myeloma

Biological and Pharmaceutical Bulletin Volume 29 Issue 11 Page 2331-2334 published_at 2006-11
アクセス数 : 640
ダウンロード数 : 190

今月のアクセス数 : 0
今月のダウンロード数 : 0
File
BiolPhamBull_29_2331.pdf 109 KB 種類 : fulltext
Title ( eng )
The Pharmacokinetics of Low-Dose Thalidomide in Japanese Patients with Refractory Multiple Myeloma
Creator
Kamikawa Rintaro
Asaoku Hideki
Iwato Koji
Sasaki Ayako
Source Title
Biological and Pharmaceutical Bulletin
Volume 29
Issue 11
Start Page 2331
End Page 2334
Abstract
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—∞), which were 45.3 l, 5.5 l/h and 21.7 μg·h/ml, respectively, with smaller Vd/F and CL/F and larger AUC0—∞ than in Caucasian populations. This pharmacokinetic difference may explain the dose difference between Japan and other countries. Adverse events were associated with AUC0—∞, 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.
Keywords
thalidomide
pharmacokinetics
multiple myeloma
NDC
Medical sciences [ 490 ]
Language
eng
Resource Type journal article
Publisher
The Pharmaceutical Society of Japan
Date of Issued 2006-11
Rights
© 2006 Pharmaceutical Society of Japan
Publish Type Version of Record
Access Rights open access
Source Identifier
[ISSN] 0918-6158
[ISSN] 1347-5215
[NCID] AA10885497
[DOI] 10.1248/bpb.29.2331
[DOI] https://doi.org/10.1248/bpb.29.2331