Premium
Effect of fluvastatin, lovastatin, nifedipine and verapamil on the systemic exposure of nateglinide in rabbits
Author(s) -
Kim Youngmin,
Park Kyemyung,
Kang Wonku
Publication year - 2010
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.724
Subject(s) - fluvastatin , nateglinide , nifedipine , pharmacology , pharmacokinetics , verapamil , felodipine , lovastatin , chemistry , pravastatin , medicine , endocrinology , cholesterol , calcium , simvastatin , diabetes mellitus , blood pressure , type 2 diabetes
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 © 2010 John Wiley & Sons, Ltd.