Effect of Fluvastatin, Lovastatin, Nifedipine and Verapamil on the Systemic Exposure of Nateglinide in Rabbits

Title
Effect of Fluvastatin, Lovastatin, Nifedipine and Verapamil on the Systemic Exposure of Nateglinide in Rabbits
Author(s)
김영민[김영민]박계명[박계명]강원구
Keywords
HUMAN-LIVER-MICROSOMES; CLINICAL PHARMACOKINETICS; HEALTHY-VOLUNTEERS; PHARMACODYNAMICS; METABOLISM; OXIDATION; AGENT; DRUG; RAT
Issue Date
201011
Publisher
JOHN WILEY & SONS LTD
Citation
BIOPHARMACEUTICS & DRUG DISPOSITION, v.31, no.8-9, pp.443 - 449
Abstract
A diabetic patient may suffer simultaneously from cardiovascular disease; thus, lipid-lowering or anti-hypertensive agents could be given together with nateglinide. The pharmacokinetics of nateglinide were investigated in the presence and absence of HMG-CoA reductase inhibitors (fluvastatin, lovastatin) and calcium channel blockers (verapamil, nifedipine) in rabbits. A pharmacokinetic modeling approach was used to quantify the effects of the drugs that significantly influenced the pharmacokinetics of nateglinide. Fluvastatin and nifedipine shifted the time course of serum nateglinide concentrations upwards; there was no significant change with verapamil or lovastatin. The C(max) and AUC(inf) increased 1.5-(p<0.05) and 1.3-fold in the presence of fluvastatin and 1.8-(p<0.01) and 2.4-fold (p<0.01) in the presence of nifedipine, respectively. In a simultaneous nonlinear regression, fluvastatin and nifedipine decreased the elimination rate constant, by 76% and 32%, respectively. Fluvastatin and nifedipine increased the systemic exposure of nateglinide in rabbits, probably due to their inhibitory action on the metabolism of nateglinide by CYP2C5 (human CYP2C9). The concomitant use of fluvastatin and/or nifedipine with nateglinide is quite likely; therefore, the clinical consequences of long-term treatments must be considered. Copyright (C) 2010 John Wiley & Sons, Ltd.
URI
http://hdl.handle.net/YU.REPOSITORY/23386http://dx.doi.org/10.1002/bdd.724
ISSN
0142-2782
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약학대학 > 약학부 > Articles
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