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Administration of AVANDAMET 4 mg/ 500 mg with food resulted in no change in overall exposure (AUC) for either rosiglitazone or metformin. However, there were decreases in Cmax of both components (22% for rosiglitazone and 15% for metformin, respectively) and a delay in
Tmax of both components (1.5 hours for rosiglitazone and 0.5 hours for metformin, respectively). These changes are not likely to be clinically significant. The pharmacokinetics of both the rosiglitazone component and the metformin component of AVANDAMET when taken with food were similar to the pharmacokinetics of rosiglitazone and metformin when administered concomitantly as separate tablets with food. Rosiglitazone maleate: Text Continues Below
The absolute bioavailability of rosiglitazone is 99%. Peak plasma concentrations are observed about 1 hour after dosing. Maximum plasma concentration (Cmax) and the area under the curve (AUC) of rosiglitazone increase in a dose-proportional manner over the therapeutic dose range. The elimination half-life is 3 to 4 hours and is independent of dose. Metformin hydrochloride The absolute bioavailability of a 500 mg metformin hydrochloride tablet given under fasting conditions is approximately 50% to 60%. Studies using
single oral doses of metformin hydrochloride tablets of 500 mg and 1,500 mg, and 850 mg to 2,550 mg, indicate that there is a lack of dose proportionality with increasing doses, which is due to decreased absorption rather than an alteration in elimination. Distribution: Rosiglitazone maleate: The mean (CV%) oral volume of distribution (Vss/ F) of rosiglitazone is approximately 17.6 (30%) liters, based on a population pharmacokinetic analysis. Rosiglitazone is approximately 99.8% bound to plasma proteins, primarily albumin. Metformin hydrochloride The apparent volume of distribution (V/ F) of metformin following single oral doses of 850 mg metformin hydrochloride averaged 654 ± 358 L. Metformin is negligibly bound to plasma proteins. Metformin partitions into erythrocytes, most likely as a function of time. At usual clinical doses and dosing schedules of metformin, steady-state plasma concentrations of metformin are reached within 24 to 48 hours and are generally <1 mcg/ mL. During controlled clinical trials, maximum metformin plasma levels did not exceed 5 mcg/ mL, even at maximum doses. Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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