Pharmacokinetics/Pharmacodynamics of Acetaminophen Analgesia in Japanese Patients with Chronic Pain(Biopharmacy)
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概要
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Acetaminophen (APAP) is a popular analgesic. In the present study, we characterized the pharmacokinetics and pharmacodynamics of APAP in the Japanese. Five healthy volunteers were administered 1000mg of APAP orally. Five patients with chronic pain were administered the optimal oral dose of APAP ranging from 600 to 1000mg to allow for an adequate analgesic effect. Plasma APAP and APAP metabolite concentrations were measured in the volunteers, plasma APAP concentrations and pain scores using a visual analog scale were measured in the patients with chronic pain. Patient data were fitted to a first-order absorption one-compartment model with delayed effects accounted for by an effect compartment. A sigmoid E_<max> model was used as the pharmacodynamic model. Acetaminophen-cysteine metabolites, which are conjugates of the toxic metabolite N-acetyl-p-benzoquinone-imine, were detected in the plasma at levels lower than 0.2μg/ml, but no side effects were observed. The pharmacokinetic and pharmacodynamic parameter (mean±S.D.) estimates were as follows: clearance, 18.7±4.7l/h; distribution volume, 30.9±6.8l; absorption rate constant, 2.4±1.3h^<-1>; rate constant for the elimination of APAP from the effect compartment, 1.3±0.5h^<-1>; maximum pain relief score, 4.6±2.2 units; effect compartment concentration at 50% maximum, 2.0±1.2μg/ml; and sigmoid factor, 1.3±0.7. These results suggest that these parameters can be used to determine an effective APAP dosage regimen for Japanese patients with chronic pain.
- 2007-01-01
著者
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MATSUMOTO Yoshiaki
Department of Clinical Pharmacology and Toxicology, Showa College of Pharmaceutical Sciences
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SHINODA Shigeo
Second Department of Anesthesiology, Toho University School of Medicine
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AOYAMA Takahiko
Department of Clinical Pharmacokinetics, College of Pharmacy, Nihon University
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AOYAMA Yukio
Second Department of Anesthesiology, Toho University School of Medicine
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TOMIOKA Sachiko
Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University
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OHE Yoko
Second Department of Anesthesiology, Toho University School of Medicine
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Ohe Yoko
Second Department Of Anesthesiology Toho University School Of Medicine
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Aoyama Yukio
Second Department Of Anesthesiology Toho University School Of Medicine
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Shinoda Shigeo
Second Department Of Anesthesiology Toho University School Of Medicine
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Aoyama Takahiko
Department Of Cardiac Surgery Aichi Medical University
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Aoyama Takahiko
Department Of Clinical Pharmacokinetics College Of Pharmacy Nihon University
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Tomioka Sachiko
Laboratory Of Drug Metabolism And Pharmacokinetics Showa Pharmaceutical University
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Matsumoto Yoshiaki
Department Of Clinical Pharmacology And Toxicology Showa Pharmaceutical University
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Matsumoto Yoshiaki
Department Of Clinical Pharmacokinetics College Of Pharmacy Nihon University
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