Metformin pharmacokinetics

In 16 male volunteers aged 22-55 years, rosiglitazone 2 mg bd had no effect on the steady-state pharmacokinetics of oral metformin 500 mg bd there were no clinically significant episodes of hypoglycemia and blood lactic acid concentrations did not increase (150). 

Scheen AJ. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 1996 30(5) 359-71. 

Pentikainen PJ, Neuvonen PJ, Penttila A. Pharmacokinetics of metformin after intravenous and oral administration to man. Em J Clin Pharmacol 1979 16(3) 195-202. 

Timmins P, Donahue S, Meeker J, Marathe P. Steady-state pharmacokinetics of a novel extended-release metformin formulation. Clin Pharmacokinet 2005 44 721-9. 

Jayasagar G, Krishna Kumar M, Chandrasekhar K, Madhusudan Rao C, Madhusudan Rao Y. Effect of cephalexin on the pharmacokinetics of metformin in healthy human volunteers. Drag Metabol Drag Interact 2002 19(l) 41-8. 

Di Cicco RA, Allen A, Carr A, Fowles S, Jorkasky DK, Freed MI. Rosiglitazone does not alter the pharmacokinetics of metformin. J Clin Pharmacol 2000 40(ll) 1280-5. 

In a placebo-controlled, multiple-dose, crossover study in 13 patients with type 2 diabetes, sitagliptin 50 mg bd and metformin 1000 mg bd did not alter the pharmacokinetics of each other (7). 

Herman GA, Bergman A, Yi B, Kipnes M The Sitagliptin Study 012 Group. Tolerability and pharmacokinetics of metformin and the dipeptidyl peptidase-4 inhibitor sitagliptin when co-administered in patients with type 2 diabetes. Curr Med Res Opin 2006 22(10) 1939 t7. 

In 16 healthy men taking metformin 500 mg bd and/or rosiglitazone 2 mg bd for 4 days there were no significant effects on the steady-state pharmacokinetics of either drug (142). 

Gusler, G., et al. 2001. Pharmacokinetics of metformin gastric-retentive tables in healthy volunteers. 

Gusler, G., Gorsline, J., Levy, G., et al. Pharmacokinetics of metformin gastric-retentive tablets in healthy volunteers. J. Clin. Pharmacol. 41(6) 655-661, 2001. 

Stepensky, D. Friedman, M. Raz, I. Hoffman, A. Pharmacokinetic-pharmacodynamic analysis of the glucose-lowering effect of metformin in diabetic rats reveals first-pass pharmacodynamic effect. Drug Metab. Dispos. 2002, 30 (8), 861-868. 

Metformin is slowly and incompletely absorbed and rapidly eliminated without hepatic metabolism. This pharmacokinetic profile may make drug accumulation and lactic acidosis less likely to occur with metformin than with other biguanides. Sales of the longer-acting biguanide phenformin (10), for instance, which is metabolized in the liver by aromatic... 

Pharmacokinetics. Metformin has approximately 50% to 60% oral bioavailability, low lipid solubility, and a volume of distribution that approximates body water. Metformin is not metabolized and does not bind to plasma proteins. Metformin is eliminated by renal tubular secretion and glomerular filtration. The average half-life of metformin is 6 hours, though pharmacodynamically, metformin s an-tihyperglycemic effects last >24 hours. 

Rosiglitazone has been studied in combination with acarbose, digoxin, metformin, nifedipine, ranitidine, warfarin, and oral contraceptives [67,72] There have been no clinically significant effects on the pharmacokinetics of any of these agents in combination with rosiglitazone. 

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%. 

Orlistat improved glycaemic control, which resulted in the need to reduce the dose of glibenclamide (glyburide) or glipizide in almost half the patients in one study. In other studies, orlistat also reduced the dose requirement for metformin and for insulin. Orlistat did not alter the pharmacokinetics of glibenclamide or metformin. Orlistat and cimetidine may have contributed to a case of metformin-associated lactic acidosis. The manufacturers recom-... 

In healthy subjects, pioglitazone 45 mg daily for 7 days did not alter the pharmacokinetics of a single 1-g dose of metformin. - ... 

The steady-state pharmacokinetics of metformin 500 mg twice daily and rosiglitazone 2 mg twice daily were not affected when they were given to healthy subjects for 4 days. ... 

The use of memantine with a combined product containing glibenclamide and metformin did not result in any changes in the pharmacokinetics of either of the three drugs. Memantine did not reduce the glucose-lowering effects of either drug. ... 

The manufacturers say that the pharmacokinetics of glibenclamide (glyburide) were not affected by a single 20-mg dose of vardenafil, and that vardenafil had no effect on glibenclamide pharmacodynamics (glucose and insulin levels). Also, although no specific pharmacokinetic study has been conducted, the manufacturers say that population pharmacokinetic analysis suggests that sulphonylureas (not named) and metformin have no effect on vardenafil pharmacokinetics. No additional precautions therefore seem necessary on concurrent use. ... 

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