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
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Title ( eng ) |
The Pharmacokinetics of Low-Dose Thalidomide in Japanese Patients with Refractory Multiple Myeloma
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Creator |
Kamikawa Rintaro
Asaoku Hideki
Iwato Koji
Sasaki Ayako
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Source Title |
Biological and Pharmaceutical Bulletin
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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.
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Keywords |
thalidomide
pharmacokinetics
multiple myeloma
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NDC |
Medical sciences [ 490 ]
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Language |
eng
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Resource Type | journal article |
Publisher |
The Pharmaceutical Society of Japan
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Date of Issued | 2006-11 |
Rights |
© 2006 Pharmaceutical Society of Japan
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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
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