Study on the interactions of pharmacokinetics and liver distributions between rosuvastatin and repaglinide in rats

doi:10.5246/jcps.2018.01.003

Abstract

Abstract:

In the present study,we aimed to investigate the interactions of pharmacokinetics and liver distributions between rosuvastatin and repaglinide in rats.Coadministration of repaglinide (0.5 mg/kg, 1 mg/kg and 2 mg/kg) for 7 d significantly increased the AUC_0–24 and C_max of rosuvastatin (P<0.01), but dramatically decreased the CL/F of rosuvastatin (P<0.01) after a single dose of rosuvastatin (10 mg/kg). There were no obviously changes in the parameters of T_maxand t_1/2. Coadministration of repaglinide also decreased the liver distribution of rosuvastatin (P<0.01). Coadministration of rosuvastatin (20 mg/kg) for 7 days significantly increased the AUC_0–12 and C_maxof repaglinide (P<0.05), and decreased the CL/F of repaglinide (P<0.01) after a single dose of repaglinide (1 mg/kg). The liver distribution of repaglinide was also decreased (P<0.01). Our animal study indicated that repaglinide could significantly affect the pharmacokinetics and liver distribution of rosuvastatin in rats and vice versa.

Key words: Rosuvastatin, Repaglinide, Pharmacokinetics, Drug-drug interaction, Liver distribution

CLC Number:

R969.1

Supporting:

Dujuan Zhang, Keguang Chen, Rui Zhang, Guiyan Yuan, Benjie Wang, Ruichen Guo. Study on the interactions of pharmacokinetics and liver distributions between rosuvastatin and repaglinide in rats[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(1): 22-30.

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