Systemic exposure to rosiglitazone is unaltered by food.
OBJECTIVE
To evaluate the effect of food on the bioavailability and pharmacokinetics of the insulin sensitizer rosiglitazone.


METHODS
In a randomized, open-label, period-balanced, single-dose, crossover study, rosiglitazone 2 mg was administered to 12 healthy male volunteers either in the fasting state or following a standard high-fat breakfast. The primary end points of the study were AUC(0-inf) and Cmax.


RESULTS
Single oral doses of rosiglitazone were safe and well tolerated. Overall exposure to rosiglitazone was unaffected by food. The geometric mean ratio of AUC(0-inf) in the fed:fasted regimens was 0.94 (95% CI: 0.82, 1.06); t1/2 was unaffected. Absorption of rosiglitazone in the fed state was more gradual and sustained than in the fasted state. Cmax was reduced by approximately 20% (point estimate 0.80; 95% CI 0.65 to 0.97) and tmax was modestly delayed in the fed state.


CONCLUSIONS
These data support dosing guidelines that will permit the administration of rosiglitazone without regard to meals for treatment of type 2 diabetes mellitus.
Freed
M I
MI
SmithKline Beecham Clinical Pharmacology Unit, Presbyterian Medical Center of the University of Pennsylvania Health System, Philadelphia 19104, USA. Martin_I_Freed@sbphrd.com
Allen
A
A
Jorkasky
D K
DK
DiCicco
R A
RA
D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000494:pharmacology*; D005215:Fasting; D018565:Food-Drug Interactions / Q000502:physiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood*; D008297:Male; D000077154:Rosiglitazone; D013844:Thiazoles / Q000009:adverse effects / Q000097:blood*; D045162:Thiazolidinediones
D004041:Dietary Fats; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D000077154:Rosiglitazone