Repaglinide pharmacokinetics

M. Niemi, J. T. Backman, L. I. Kajosaari, J. B. Leathart, M. Neuvonen, A. K. Daly, M. Eichelbaum, K. T. Kivisto, and P. J. Neuvonen. Polymorphic organic anion transporting polypeptide IB 1 is a major determinant of repaglinide pharmacokinetics. Clin Pharmacol Ther 77 468-478 (2005). 

Hatorp V, Huang WC, Strange P. Repaglinide pharmacokinetics in healthy young adult and elderly subjects. Clin Ther 1999 21(4) 702-10. 

Hatorp V, Thomsen MS. Drug interaction studies with repaglinide repaglinide on digoxin or theophylline pharmacokinetics and cimetidine on repaglinide pharmacokinetics. J Clin Pharmacol 2000 40(2) 184-92. 

Niemi M, Backman JT, Kajosaari LI, et al. Polymorphic organic anion transporting polypeptide 1B1 is a major determinant of repaglinide pharmacokinetics. Clin Pharmacol Ther 2005 77 468-478. 

B1 is a major determinant of repaglinide pharmacokinetics. Clinical Pharmacology and Therapeutics, 77, 468—478. 

CYP2C8 Repaglinide Pharmacokinetic parameters 3 associated with lower plasma concentrations 46... 

The modest changes in repaglinide pharmacokinetics with ketoconazole and itraconazole may be because repaglinide is metabolised by both CYP2C8 and CYP3A4, and one pathway may have the capacity to compensate if the other is inhibited. Similarly, itraconazole modestly affects nateglinide metabolism via CYP3A4. ... 

Cimetidine appears to reduce the clearance of metformin, and may have contributed to a case of metformin-associated lactic acidosis. Cimetidine did not alter repaglinide pharmacokinetics, and ranitidine did not alter pioglitazone or rosiglitazone pharmacokinetics. Acarbose did not alter ranitidine pharmacokinetics, but miglitol decreased the AUC of ranitidine by 60%. 

Tornio A, Niemi M, Neuvonen M, Laitila J, Kalliokoski A, Neuvonen PJ, Backman JT. The effect of gemfibrozil on repaglinide pharmacokinetics persists for at least 12 h after the dose evidence for mechanism-based inhibition of CYP2C8 in vivo. Chn Pharmacol Ther 2008 84 403-11. 

When the pharmacokinetics of repaglinide 0.5, 1.0, and 2.0 mg were studied in healthy men, 15 Caucasians and 12 Japanese, AUC and Cmax were higher in the Japanese (53). 

However, in a formal study bezafibrate and fenofibrate did not affect the pharmacokinetics or pharmacodynamics of a single dose of repaglinide 0.25 mg (63). 

Studies involving rifampicin and repaglinide have yielded conflicting results, perhaps because of timing and dosages. In one study rifampicin had no effect on the pharmacokinetics and pharmacodynamics of a single dose repaglinide... 

Thomsen MS, Chassard D, Evene E, Nielsen KK, Jprgensen M. Pharmacokinetics of repaglinide in healthy Caucasian and Japanese subjects. J Clin Pharmacol 2003 43 23-8. 

Schumacher S, Abbasi I, Weise D, Hatorp V, Sattler K, Sieber J, Hasslacher C. Single- and multiple-dose pharmacokinetics of repaglinide in patients with type 2 diabetes and renal impairment. Eur J Clin Pharmacol 2001 57(2) 147-52. 

Anonymous. Clinical news. Interactions and pharmacokinetics of repaglinide. Pharm J 2000 264 503. 

Niemi M, Backman JT, Neuvonen M, Neuvonen PJ. Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide potentially hazardous interaction between gemfibrozil and repaglinide. Diabetologia 2003 46(3) 347-51. 

Hatorp V, Hansen KT, Thomsen MS. Influence of drugs interacting with CYP3 A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide. J Clin Pharmacol 2003 43(6) 649-60. 

In a double-blind, placebo-controlled study in 28 healthy subjects who were stabilised on warfarin, repaglinide did not alter the anticoagulant effects of warfarin or the steady-state warfarin pharmacokinetics. Therefore, no warfarin dosage adjustment would be anticipated on concurrent use. 

Rosenberg M, Strarge P, Cohen A Assessment of pharmacokinetic (PK) and iharmacody-namic (PD) interaction between warfarin and repaglinide Diabetes ( 9 )4S (Suppl 1), A356. 

Itraconazole also appears not to affect diabetic control in most patients, but there are reports of hypoglycaemia or hyperglycaemia associated with its use. Itraconazole causes modest increases in repaglinide and nateglinide levels, but has no effect on pioglita-zone pharmacokinetics. Ketoconazole increases the blood glu-... 

---