흰쥐에서 베라파밀과 장기투여된 피오그리타존과의 약물상호작용
Drug Interaction Between Verapamil and Pioglitazone Long-term Administered to Rats
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This study investigated the effect of long-term administration of pioglitazone on the pharmacokinetics of verapamil in rats. Pharmacokinetic parameters of verapamil were determined after oral administration of verapamil (9 mg/kg) in rats coadministered pioglitazone (0.5 mg/kg) or pretreated with pioglitazone (0.5 mg/kg) for 3 and 9 days. Compared to oral control group, the presence of pioglitazone significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC) of verapamil by 48.6% (coad), 61.1% (3 days) and 56.5% (9 days), and the peak concentration (Cmax) by 65.1% (coad), 76.8% (3 days) and 66.4% (9 days). The absolute bioavailability (AB%) of verapamil was significantly (p<0.05) higher by 6.2% (coad), 6.7% (3 days), 6.5% (9 days) compared to control (4.2%), and presence of pioglitazone was no significant change in the terminal half-life (t1/2) and the time to reach the peak concentration (Tmax) of verapamil. Our results indicate that pioglitazone significantly enhanced oral bioavailability of verapamil in rats, implying that presence of pioglitazone could be effective to inhibit the CYP3A4-mediated metabolism of verapamil in the intestine. Drug interactions should be considered in the clinical setting when verapamil is coadministrated with pioglitazone.
Abstract
This study investigated the effect of long-term administration of pioglitazone on the pharmacokinetics of verapamil in rats. Pharmacokinetic parameters of verapamil were determined after oral administration of verapamil (9 mg/kg) in rats coadministered pioglitazone (0.5 mg/kg) or pretreated with pioglitazone (0.5 mg/kg) for 3 and 9 days. Compared to oral control group, the presence of pioglitazone significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC) of verapamil by 48.6% (coad), 61.1% (3 days) and 56.5% (9 days), and the peak concentration (Cmax) by 65.1% (coad), 76.8% (3 days) and 66.4% (9 days). The absolute bioavailability (AB%) of verapamil was significantly (p<0.05) higher by 6.2% (coad), 6.7% (3 days), 6.5% (9 days) compared to control (4.2%), and presence of pioglitazone was no significant change in the terminal half-life (t1/2) and the time to reach the peak concentration (Tmax) of verapamil. Our results indicate that pioglitazone significantly enhanced oral bioavailability of verapamil in rats, implying that presence of pioglitazone could be effective to inhibit the CYP3A4-mediated metabolism of verapamil in the intestine. Drug interactions should be considered in the clinical setting when verapamil is coadministrated with pioglitazone.
참고문헌 (36)
- Fleckenstein A, "Specific pharmacology of calcium in myocardium. cardiac pacemakers, and vascular smooth muscle", Ann Rev Pharmacol Toxicol, 17, pp.149~166 (1977)
- Krikler DM, "verapamil in the treatment of paroxysmal supraventricular tachycardias", Postgrad Med J, 50, pp.447~453 (1974)
- Gould BA, "Bala Subramanian V, Raftery EB. The 24-hour ambulatory blood pressure profile with verapamil", Circulation, 65, pp.22~27 (1982)
- Lewis GRJ, "The treatment of hypertension with verapamil", N.Z. Med J, 87, pp.351~354 (1978)
- Schomerus M, "Physiologic disposition of verapamil in man", Cardiovasc Res, 10, pp.605~612 (1976)
- Neugebauer G, "Comparative cardiovascular actions of verapamil and its major metabolites in the anesthetized dog", Cardiovasc Res, 12, pp.247~254 (1978)
- Eichelbaum M, "The metabolism of D,L(14C) verapamil in man", Drug Metab Dispos, 7, pp.145~148 (1979)
- Eichelbaum M, "Pharmacokinetics of (+)-,(−�)- and (±)-verapamil after intravenous administration", Br J Clin Pharmacol, 17, pp.453~458 (1984)
- Woodcock BG, "Verapamil disposition in liver disease and intensive-case patients: kinetics, clearance and apparent blood flow relationships", Clin Pharmacol Ther, 29, pp.27~34 (1981)
- Eichelbaum M, "Influence of mesocaval shunt surgery on verapamil kinetics, bioavailability and response", Br J Clin Pharmacol, 10, pp.527~529 (1980)
- Schwartz JB, "An investigation of the cause of accumulation of verapamil during regular dosing in patients", Br J Clin Pharmacol, 19, pp.512~156 (1985)
- Freedman SB, "Verapamil kinetics in normal subjects and patients with coronary artery spasm", Clin Pharmacol Ther, 30, pp.644~652 (1981)
- Eichelbaum M, "Effects of verapamil on PR intervals in relation to verapamil plasma levels following single i.v. and oral administration and during chronic treatment", Klinische Wochenschrift, 58, pp.919~925 (1980)
- Mikus G, "Die Anwendung eines mit stabilen isotopen markierten Arzneimittels zur simultanen Bestimmung der relativen biologischemVerfugbarkeit einer verapamil retard", 석사, pp.1985
- Dominic JA, "The pharmacology of verapamil. III. Pharmacokinetics in normal subjects after intravenous drug administration", J Cardiovasc Pharmacol, 3, pp.25~38 (1981)
- McAllister RG, "Clinical pharmacology of slow channel blocking agents", Pro Cardiovasc Diseas, 25, pp.83~102 (1982)
- McGowan FX, "Verapamil plasma binding: Relationship to alpha1-acid glycoprotein and drug efficacy", Clin Pharmacol Ther, 33, pp.485~490 (1983)
- Keefe DL, "Verapamil protein binding in patients and in normal subjects", Clin Pharm Ther, 29, pp.21~26 (1981)
- Loi CM, "Effect of cimetidine on verapamil disposition", Clin Pharm Ther, 37, pp.654~657 (1985)
- Johnson LM, "The influence of cimetidine on the pharmacokinetics of the enantiomers of verapamil in the dog during multiple oral dosing", J Vet Pharmacol Ther, 18, pp.117~123 (1995)
- Ho PC, "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of verapamil enantiomers in healthy volunteers", Eur J Clin Pharmacol, 56, pp.693~698 (2000)
- Fuhr U, "Effect of grapefruit juice and smoking on verapamil concentration steady state", Eur J Clin Pharmacol, 58, pp.45~53 (2002)
- Sandstrom R, "Jejunal absorption and metabolism of R", S-verapamil in humans, 1998, pp.15, 856~862
- Wacher VJ, "Overlapping substrate specificities and tissue distribution of cytochrome p450 3A and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy", Mol Carcinog, 13, pp.129~134 (1995)
- Chilcott J, "A systematic review of the clinical effectiveness of pioglitazone in the treatment of type 2 diabetes mellitus", Clin Ther, 23, pp.1792~823 (2001)
- Lehmann JM, "An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma)", J Biol Chem, 270, pp.12953~12956 (1995)
- Lowell BB, "PPAR gamma: an essential regulator of adipogenesis and modulator of fat cell function", Cell, 99, pp.239~242 (1999)
- Spiegelman BM, "Adipogenesis and obesity: rounding out the big picture", Cell, 87, pp.377~389 (1996)
- Walsky RL, "Examination of 209 drugs for inhibition of cytochrome P450 2C8", J Clin Pharmacol, 45, pp.68~78 (2005)
- Sahi J, "Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition", Drug Metab Dispos, 31, pp.439~446 (2003)
- Kajosaari LI, "Pioglitazone, an in vitro inhibitor of CYP2C8 and CYP3A4, does not increase the plasma concentrations of the CYP2C8 and CYP3A4 substrate repaglinide", Eur J Clin Pharmacol, 62, pp.217~223 (2006)
- Choi DH, "Effect of atorvastatin on the intravenous and oral pharmacokinetics of verapamil in rats", Biopharm Drug Dispos, 29, pp.45~50 (2008)
- Wittayalertpanya S, "The pharmacokinetics of pioglitazone in Thai healthy subjects", J Med Assoc Thai, 89, pp.2116~2122 (2006)
- 식품의약품안전청, "생물학적동등성시험 표준지침", pp.142~146 (2003), 식품의약품안전청
- Kim HJ, "Effects of naringin on the pharmacokinetics of verapamil and one of its metabolites, norverapamil, in rabbits. Biopharm", Drug Dispos, 26, pp.295~300 (2005)
- Choi JS, "The effect of quercetin on the pharmacokinetics of verapamil and its major metabolite, norverapamil, in rabbits", J. Pharm. Pharmacol, 56, pp.1537~1542 (2004)
