A Simple Method for the Simulation of Unbound Serum Disopyramide Concentration in Patients

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概要

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• There were remarkable differences in the serum total and unbound concentrations of disopyramide (DP) and mono-N-dealkyldisopyramide (MND), the major metabolite of DP, among patients with arrhythmias. Serum levels of α_1-acid glycoprotein (AAG) also varied among the same patients. To predict the unbound DP concentrations, we have obtained the serum concentration-time curves of unbound DP in these patients by means of total DP concentration, DP pharmacokinetic parameters, AAG levels and dissociation constants of DP and MND at specific AAG binding sites. In patients with normal AAG levels, the theoretical values of unbound DP were in good agreement with the measured concentrations. On the other hand, in patients with high AAG levels, the theoretical values could be obtained by correcting the calculated values using both AAG levels of each patient and the equation correlating the unbound DP fraction to AAG concentrations. These findings indicate that patient AAG levels can provide valuable information permitting the rapid estimation of unbound DP concentrations, the pharmacologically active fraction, and the development of effective DP dosage regimens.

• 社団法人日本薬学会の論文

著者

• Kobayashi Michiya

  北海道大学医学部附属病院 薬剤

• KISHINO Satoshi

  Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University

• YASUDA HISAKAZU

  Department of Cardiovascular Medicine, Hokkaido University School of Medicine

• Iseki Ken

  Department Of Clinical Pharmaceutics And Therapeutics Graduate School-of Pharmaceutical Sciences Hok

• Iseki Ken

  Department Of Cell Science Institute Of Biomedical Sciences Fukushima Medical University School Of M

• MIYAZAKI Katsumi

  Department of Pharmacy, Hokkaido University Hospital Sapporo

• NOMURA Akikazu

  Department of Cardiovascular Medicine, School of Medicine, Hokkaido University

• KOHRI NAONORI

  Department of Pharmacy, Hokkaido University Hospital

• Kishino S

  Hokkaido Univ. Sapporo Jpn

• Kishino Satoshi

  Department Of Medication Use Analysis And Clinical Research Meiji Pharmaceutical University

• Yasuda Hisakazu

  Department Of Cardiology Hokkaido University School Of Medicine Sapporo

• Yasuda Hisakazu

  Department Of Pharmacy:department Of Cardiovascular Medicine Hokkaido University Hospital School Of

• Nomura Akikazu

  Department Of Pathophysiology Hokkaido College Of Pharmacy

• Nomura Akikazu

  Department Of Cardiovascular Medicine Hokkaido University School Of Medicine

• Kohri Naonori

  Department Of Pharmacy:department Of Cardiovascular Medicine Hokkaido University Hospital School Of

• Kohri Naonori

  Department Of Pharmacy Hokkaido University Hospital

• Miyazaki Katsumi

  Department Of Pharmacy Hokkaido University Hospital School Of Medicine Hokkaido University

• Nomura A

  Department Of Pathophysiology Hokkaido College Of Pharmacy

• Yasuda Hisakazu

  Department Of Cardiology Hokkaido University School Of Medicine

• Yasuda Hisakazu

  Department O F Cardiovascular Medicine Hokkaido University School Of Medicine

• Miyazaki Katsumi

  Department of Biology, Keio University

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