マクロライド系抗生物質による相互作用誘発危険性の比較評価 : 各種文献データの遡及的統合

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Although macrolide antibiotics are known to elicit a pharmacokinetic interaction with other various agents via the inhibition of oxidative metabolism by P 450, the inducibilities of drug-interaction have yet to be quantitatively compared among various macrolides. To quantitatively compare these incidences, we collected the findings of various reports in order to analyze and integrate them retrospectively. We chosed reports referring to the area under the curve (AUC) value in human after the oral administration of carbamazepine, cyclosporine, felodipine, midazolam or terfenadine, which is known to be metabolized by P 450 3 A 4, alone and with macrolides. The decreases in oral clearance (ΔCLp.o.) evoked by macrolides were calculated according to the increase in AUC by the concomitant administration of macrolides. In the 23 collected reports, erythromycin (EM), clarithromycin (CAM), azithromycin (AZM), miocamycin (MDM) and roxithromycin (RXM) were referred to in 13, 2, 6, 2 and 2 reports, respectively. Other macrolides, were only referred to in one report. The ΔCLp.o. values of the five macrolides noted above, i.e. EM, CAM, AZM, MDM and RXM were 51.0 ± 18.1, 66.3 ± 8.1, 5.8 ± 13.6, 29.4 ± 23.5 and 11.1 ± 29.5% (mean ± S.D.) , respectively. The ΔCLp.o. that of AZM was significantly smaller than of EM and CAM (p<0.001 and p<0.01, respectively ; by ANOVA and Bonferroni multiple comparison test). In conclusion, based on a retrospective analysis of the pharmacokinetic data in literature, AZM may be less effective for eliciting a pharmacokinetic drug-interaction. As a result, AZM might have some advantages over EM or CAM for avoiding of drug-interaction.
日本医療薬学会の論文
1998-06-10

マクロライド系抗生物質による相互作用誘発危険性の比較評価 : 各種文献データの遡及的統合

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