ミダゾラムの肝薬物代謝に関する相互作用の定量的予測

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  • Quantitative prediction of the interaction on hepatic metabolism of midazolam

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(1) We tried to predict the increase rate (F) of plasma concentration or miaazolam (MDZ) in the presence of inhibitors in rats, using the following equation. F=1+Ci/Ki (Ci:concentration of inhibitor, Ki:inhibitory constant). The predicted F in the presence of itraconazole, ketoconazole, cimetidine, and nizatidine using unbound concentrations of inhibitors in the liver were close to the observed values, suggesting the concentrative uptake of inhibitors into the liver must be taken into consideration to predict F. (2) There was a good correlation between the cell-to-medium concentration ratio (C/M) and the liver-to-unbound plasma concentration ratio (Kpf) in rats, suggesting drug concentration in the liver can be predicted from C/M and unbound plasma concentration. (3) We attemptted to predict F of plasma concentration of MDZ in the presence of inhibitors in human from absorption constant and Kpf in rats. The predicted F in the presence of cimetidine corresponded to the observed value.

収録刊行物

  • 薬物動態

    薬物動態 12 (supplement), 134-135, 1997

    日本薬物動態学会

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