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药代动力学感染在酮康唑和吡喹酮之间健康志愿者.pdf

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药代动力学感染在酮康唑和吡喹酮之间健康志愿者

Journal of Clinical Pharmacy and Therapeutics (2007) 32, 585–593 ORIGINAL ARTICLE Pharmacokinetic interaction between ketoconazole and praziquantel in healthy volunteers W. Ridtitid* MD FRCFPT, K. Ratsamemonthon MSc, W. Mahatthanatrakul* MD FRCFPT and M. Wongnawa* MSc *Clinical Pharmacology Laboratory, Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, Thailand and Division of Pharmacy, Rattaphom Community Hospital, Rattaphom, Songkhla, Thailand (955Æ94 ± 307Æ74 vs. 1843Æ10 ± 336Æ39 ng h⁄ mL; SUMMARY P 0Æ01) and 102% (183Æ38 ± 43Æ90 vs. 371Æ31 ± Background: Praziquantel, a broad-spectrum 44Æ63 ng⁄ mL; P 0Æ01), respectively, whereas the anthelminthic, has been reported to undergo mean total clearance (Cl⁄ F) of praziquantel was extensive ﬁrst-pass metabolism by cytochrome signiﬁcantly decreased by 58% (2Æ65 ± 0Æ64 vs. P450 (CYP) enzymes in vivo. Ketoconazole, a 1Æ11 ± 0Æ35 mL⁄ h⁄ kg; P 0Æ01). potent CYP3A4 inhibitor, is known to markedly Conclusion: Ketoconazole co-administration alters increase plasma concentrations of many the pharmacokinetics of praziquantel in humans, co-administered drugs. However, no data are possibly through inhibition of CYP3A, particu- available on the potential pharmacokinetic drug larly CYP3A4, ﬁrst-pass metabolism of praziqu- interaction between ketoconazole and praziqu- antel. Our data suggest that when praziquantel is antel in humans. co-administered with ketoconazole, the dose of Objective: To investigate the potential pharma-