Pharmacokinetic interaction between fluvastatin and diltiazem in rats.
The present study aimed to investigate the effect of fluvastatin on the pharmacokinetics of diltiazem in rats. Pharmacokinetic parameters of diltiazem were determined in rats following an oral administration of diltiazem (15 mg/kg) in the presence and absence of fluvastatin (0.6 and 2.0 mg/kg). Compared with the control given diltiazem alone, the C(max) and AUC of diltiazem increased by 30-70% in rats with the concurrent use of fluvastatin, while there was no significant change in T(max) and the plasma half-life (T(1/2)) of diltiazem. Consequently, absolute and relative bioavailability values of diltiazem in the presence of fluvastatin were significantly higher (p<0.05) than those from the control group, implying that fluvastatin could reduce the presystemic extraction of diltiazem. In conclusion, the concurrent use of fluvastatin significantly enhanced the oral exposure of diltiazem in rats.
Choi
Jun-Shik
JS
College of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-Gu, Gwangju, Korea.
Piao
Yong-Ji
YJ
Han
Hyo-Kyung
HK
D000818:Animals; D019540:Area Under Curve; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004110:Diltiazem / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D065607:Cytochrome P-450 Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D000077340:Fluvastatin; D003577:Cytochrome P-450 Enzyme System; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A; D004110:Diltiazem