家兎におけるアセトアミノフェン坐剤の途中排出後の薬物体内動態の変化

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In an attempt to construct the rational use of suppositories, we developed an experimental method for the discharge of suppositories from rabbit rectum, and investigated the change of the pharmacokinetic behavior of the drug subsequent to discharge. Acetaminophen (ACA) was chosen as the model drug. The plasma concentration of ACA reached the maximum (C_<max>: 25 μg/ml) at 17 minutes after rectal administration of one commercially available suppository containing 100 mg of ACA. When the suppository was discharged from the rectum at I and 3 minutes after insertion using the pre-inserted device, the C_<;max> decreased markedly (4.5 and 11 μg/ml, respectively). However, the plasma concentration of ACA still increased even after discharge at I or 3 minutes after insertion, with their times required to reach the peak concentration being 7 and 9 minutes, respectively. Developed for the pharmacokinetic analysis of the plasma concentration after the discharge of suppository from the rectum was a pharmacokinetic model involving the assumption that only the undissolved portion (solid) of the suppository was discharged from the rectum and the dissolved portion (solution) remained. Consequently, the observed plasma concentrations well coincided with the predicted values. In conclusion, the experimental method employing the device for the artificial discharge of the suppository from the rectum should be a useful model for depicting suppository discharge from the rectum. Accordingly, the drug remaining in the rectum (dissolved portion) following the discharge of suppositories from the rectum should be considered.
日本医療薬学会の論文
1994-08-20

家兎におけるアセトアミノフェン坐剤の途中排出後の薬物体内動態の変化

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