Avandamet

[rosiglitazone maleate and metformin HCl]

Metformin hydrochloride is an antihyperglycemic agent, which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents.

Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and increases peripheral glucose uptake and utilization. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects (except in special circumstances, see PRECAUTIONS) and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.

Pharmacokinetics:

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Absorption and Bioavailability:

AVANDAMET: In a bioequivalence and dose proportionality study of AVANDAMET 4 mg/ 500 mg, both the rosiglitazone component and the metformin component were bioequivalent to coadministered 4 mg rosiglitazone maleate tablet and 500 mg metformin hydrochloride tablet under fasted conditions (see Table 1). In this study, dose proportionality of rosiglitazone in the combination formulations of 1 mg/ 500 mg and 4 mg/ 500 mg was demonstrated.

Table 1. Mean (SD) Pharmacokinetic Parameters for Rosiglitazone and Metformin Pharmacokinetic Parameter
Regimen N
AUC0-inf
(ng. h/ mL)
Cmax
(ng/ mL)
Tmax* (h) T 1/2
(h)
Rosiglitazone
A 25 1,442
(324)
242
(70)
0.95
(0.48-2.47)
4.26
(1.18)
B 25 1,398
(340)
254
(69)
0.57
(0.43-2.58)
3.95
(0.81)
C 24 349
(91)
63.0
(15.0)
0.57
(0.47-1.45)
3.87
(0.88)
Metformin
A 25 7,116
(2,096)
1,106
(329)
2.97
(1.02-4.02)
3.46
(0.96)
B 25 7,413
(1,838)
1,135
(253)
2.50
(1.03-3.98)
3.36
(0.54)
C 24 6,945
(2,045)
1,080
(327) 2.97 (1.00-5.98) 3.35 (0.59)
*Median and range presented for Tmax Regimen Key: Regimen A = 4 mg/ 500 mg AVANDAMET Regimen B = 4 mg rosiglitazone maleate tablet + 500 mg metformin hydrochloride tablet Regimen C = 1 mg/ 500 mg

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