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YIN Xinjuan, YANG Yan, TIAN Yuan, TIAN Jixin, YU Pei, ZHANG Zunjian. Effect of simvastatin on the metabolism and pharmacokinetics of felodipine in rats[J]. Journal of China Pharmaceutical University, 2014, 45(4): 450-455. DOI: 10.11665/j.issn.1000-5048.20140412
Citation: YIN Xinjuan, YANG Yan, TIAN Yuan, TIAN Jixin, YU Pei, ZHANG Zunjian. Effect of simvastatin on the metabolism and pharmacokinetics of felodipine in rats[J]. Journal of China Pharmaceutical University, 2014, 45(4): 450-455. DOI: 10.11665/j.issn.1000-5048.20140412

Effect of simvastatin on the metabolism and pharmacokinetics of felodipine in rats

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  • Felodipine has been widely coadministered with simvastatin for the treatment of cardiovascular disease(CVD). However, in vitro and in vivo interactions between them have not been systemically understood. Herein, the effects of simvastatin on the in vitro metabolism and oral pharmacokinetic profile of felodipine were investigated. Felodipine was incubated in rat liver microsomes(RLMs)with or without simvastatin. Simvastatin was found to be a non-competitive inhibitor(inhibition constant(Ki): (9. 86±0. 27)μmol/L). Following oral combination of felodipine and simvastatin, the peak plasma concentration(cmax)and area under the plasma concentration-time curve(AUC0-∞)of felodipine increased significantly, and the clearance(CLz/F)decreased obviously, while the mean residence time(MRT0-∞)and biological half-life(t1/2)were not statistically different. The altered pharmacokinetic profile of felodipine was probably due to the promoting effect of simvastatin on felodipine absorption. These findings provide some useful information for possible drug-drug interactions(DDIs)in rats, which should be paid particular attention to when felodipine and simvastatin are coadministered in clinical.
  • [1]
    Ljung B.Vascular selectivity of felodipine[J].Drugs,1985,29(2):46-58.
    [2]
    Little WC,Cheng CP,Elvelin L,et al.Vascular selective calcium entry blockers in the treatment of cardiovascular disorders:focus on felodipine[J].Cardiovasc Drug Ther,1995,9(5):657-663.
    [3]
    Saltiel E,Ellrodt AG,Monk JP,et al.Felodipine[J].Drugs,1988,36(4):387-428.
    [4]
    Cowie MR.Simultaneous treatment of hypertension and dyslipidaemia may help to reduce overall cardiovascular risk:focus on amlodipine/atorvastatin single-pill therapy[J].Int J Clin Pract,2005,59(7):839-846.
    [5]
    Wong ND,Teng W,Abrahamson D,et al.Noninvasive tracking of coronary atherosclerosis by electron beam computed tomography:rationale and design of the Felodipine Atherosclerosis Prevention Study(FAPS)[J].Am J Cardiol,1995,76(17):1 239-1 242.
    [6]
    Zheng Q,Chen X,Guo C.The effect on essential hypertension left ventricular hypertrophy with combined usage of felodipine and fluvastatin[J].China Prac Med,2011,6(8):22-23.
    [7]
    Lennernäs H,Fager G.Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors[J].Clin Pharmacokinet,1997,32(5):403-425.
    [8]
    Graham MJ, Lake BG. Induction of drug metabolism: species differences and toxicological relevance[J].Toxicology,2008,254(3):184-191.
    [9]
    Bailey DG,Bend JR,Arnold JMO,et al.Erythromycin-felodipine interaction:Magnitude,mechanism,and comparison with grapefruit juice[J].Clin Pharmacol Ther,1996,60(1):25-33.
    [10]
    Cummins CL,Jacobsen W,Benet LZ.Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4[J].J Pharmacol Exp Ther,2002,300(3):1 036-1 045.
    [11]
    Bailey DG,Arnold JMO,Munoz C,et al.Grapefruit juice-felodipine interaction:mechanism,predictability,and effect of naringin[J].Clin Pharmacol Ther,1993,53(6):637-642.
    [12]
    Neuvonen PJ,Backman JT,Niemi M.Pharmacokinetic comparison of the potential over-the-counter statins simvastatin,lovastatin,fluvastatin and pravastatin[J].Clin Pharmacokinet,2008,47(7):463-474.
    [13]
    Tian JX,Peng C,Xu L,et al.In vitro metabolism study of Strychnos alkaloids using high-performance liquid chromatography combined with hybrid ion trap/time-of-flight mass spectrometry[J].Biomed Chromatogr,2013,27(6):775-783.
    [14]
    Bradford MM.A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of proteindye binding[J].Anal Biochem,1976,72(1):248-254.
    [15]
    Reagan-Shaw S,Nihal M,Ahmad N.Dose translation from animal to human studies revisited[J].The FASEB J,2008,22(3):659-661.
    [16]
    Dixon M.The determination of enzyme inhibitor constants[J].Biochem J,1953,55(1):170-171.
    [17]
    Kallem RR,Ramesh M,Seshagirirao J.Validated LC-ESI-MS/MS method for simultaneous quantitation of felodipine and metoprolol in rat plasma:application to a pharmacokinetic study in rats[J].Biomed Chromatogr,2013,27(6):784-791.
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