Publication | Closed Access
Metabolic Fate of Pitavastatin (NK-104), a New Inhibitor of 3-Hydroxy-3-methyllutaryl Coenzyme A Reductase
32
Citations
0
References
2011
Year
Metabolic FatePitavastatin MetabolismMetabolomic ProfilingPharmacotherapyMetabolic RemodelingNew InhibitorPitavastatin GroupBiosynthesisHepatotoxicityBiochemistryMetabolic ControlMetabolomicsPharmacologyDrug-induced Liver InjuryEnergy MetabolismMetabolic RegulationMetabolismMedicinePharmacokineticsCyp2c9 PolymorphismDrug Discovery
Pitavastatin (CAS 147526-32-7, NK-104) is a new and very potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and has been approved for treatment of hyperlipoproteinaemia. Pitavastatin has been studied for its effects on hepatic microsomal drug metabolism in rats, and the activities of several drug-metabolizing enzymes have been measured. No induction of the drug metabolizing enzymes (aniline hydroxylase, aminopyrine N-demethylase, 7-ethoxycoumarin O-deethylase and UDP-glucuronic acid transferase) was found in the pitavastatin group compared to the control after the multiple administrations of pitavastatin at the dosage of 1-10 mg/kg per day for 7 days. Based on several different in vitro approaches, it is concluded that CYP2C9 is the enzyme responsible for the metabolism of pitavastatin and no metabolite is present in renal and intestinal microsomes. The CYP2C9 polymorphism was not involved in the pitavastatin metabolism. No inhibitory effect in CYP-mediated metabolism was detected on the tolbutamide 4-hydroxylation (CYP2C9) and testosterone 6 beta-hydroxylation (CYP3A4) in the presence of pitavastatin. The results suggested that pitavastatin did not affect the drug-metabolizing systems.