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Pitavastatin Concentrations Are Not Increased by CYP3A4 Inhibitor Itraconazole in Healthy Subjects
Author(s) -
Nakagawa Shunji,
Gosho Masahiko,
Inazu Yuji,
Hounslow Neil
Publication year - 2013
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.19
Subject(s) - pitavastatin , itraconazole , pharmacology , medicine , cyp3a4 , pharmacokinetics , pharmacodynamics , atorvastatin , cytochrome p450 , metabolism , antifungal , dermatology
Itraconazole is a synthetic triazole antifungal agent which is known to be a potent inhibitor of cytochrome P450 (CYP) 3A4, and may cause drug–drug interactions with the many drugs metabolized by this route, including some statins. In this study, the influence of concomitant administration of a single oral dose of pitavastatin with itraconazole at steady state was investigated to determine the potential for pharmacokinetic interaction and any effects on safety. Eighteen subjects were enrolled into the study. The AUC and C max of pitavastatin alone were 138 ng h/mL and 63.8 ng/mL, and pitavastatin with itraconazole were 106 ng h/mL and 49.5 ng/mL, respectively. Comparison of the 90% confidence interval of the geometric mean ratio of AUC 0–t and C max against a standard reference of 0.80–1.25 demonstrated that the lower limit was breached for both pitavastatin and its lactone metabolite (0.71–0.84 and 0.69–0.88 for AUC 0–t and C max , respectively, for pitavastatin, 0.86–0.97 and 0.76–0.86 for AUC 0–t and C max , respectively, for pitavastatin lactone). The safety and tolerability of pitavastatin was not affected by co‐administration with itraconazole. This study suggests that pitavastatin is not a CYP3A4 substrate in humans.