The Pharmacokinetics of Low-Dose Thalidomide in Japanese Patients with Refractory Multiple Myeloma(Biopharmacy)
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概要
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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 100mg 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 14d, the dose was increased to 200mg. The average apparent volume of distribution (Vd/F), apparent total clearance (CLIP) and area under the plasma concentration-time curve from 0 to infinity (AUC_<0-∞>), which were 45.31, 5.51/h and 21.7μg・h/ml, respectively, with smaller Vd/F and CL/F and larger AUC_<0-∞> than in Caucasian populations. This pharmacokinetic difference may explain the dose difference between Japan and other countries. Adverse events were associated with AUC_<0-∞>, which was best correlated with plasma concentration at 12h after administration. The 12-h time point was suggested to be a capable indicator for "safety-oriented" therapeutic drug monitoring of thalidomide.
- 公益社団法人日本薬学会の論文
- 2006-11-01
著者
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Asaoku Hideki
広島赤十字原爆病院 薬剤部
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Asaoku Hideki
Department Of Clinical Laboratory Hiroshima Red Cross Hospital And Atomic-bomb Survivors Hospital
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Sasaki Ayako
Department Of Pediatrics Yamagata University School Of Medicine
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Iwato Koji
Department Of Blood Transfusion Hiroshima Red Cross Hospital And Atomic-bomb Survivors Hospital
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Ikawa Kazuro
Department Of Clinical Pharmacotherapy Graduate School Of Biomedical Sciences Hiroshima University
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MORIKAWA Norifumi
Department of Clinical Pharmacotherapy, Division of Clinical Pharmacotherapeutics, Graduate School o
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Sasaki Ayako
Department Of Biofunctional Science Faculty Of Agriculture And Life Science Hirosaki University
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Sasaki Ayako
Department Of Internal Medicine Motonaga Hospital
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KAMIKAWA Rintaro
Department of Pharmacy, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital
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Kamikawa Rintaro
Department Of Pharmacy Hiroshima Red Cross Hospital And Atomic-bomb Survivors Hospital
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Morikawa Norifumi
Department Of Clinical Pharmacotherapy Graduate School Of Biomedical Sciences Hiroshima University
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Ikawa Kazuro
Department Of Clinical Pharmacotherapy Hiroshima University
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Ikawa Kazuro
Department Of Clinical Pharmacotherapy Division Of Clinical Pharmacotherapeutics Graduate School Of
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IWATO Koji
Department of Blood Transfusion, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital
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