M I Freed1, A Allen, D K Jorkasky, R A DiCicco. 1. SmithKline Beecham Clinical Pharmacology Unit, Presbyterian Medical Center of the University of Pennsylvania Health System, Philadelphia 19104, USA. Martin_I_Freed@sbphrd.com
Abstract
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. CONCLUSION: These data support dosing guidelines that will permit the administration of rosiglitazone without regard to meals for treatment of type 2 diabetes mellitus.
RCT Entities:
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. CONCLUSION: These data support dosing guidelines that will permit the administration of rosiglitazone without regard to meals for treatment of type 2 diabetes mellitus.
Authors: Daniel L Hertz; Christine M Walko; Arlene S Bridges; J Heyward Hull; Jill Herendeen; Kristan Rollins; Paul B Watkins; E Claire Dees Journal: Br J Clin Pharmacol Date: 2012-07 Impact factor: 4.335
Authors: Dipak Panigrahy; Samuel Singer; Lucy Q Shen; Catherine E Butterfield; Deborah A Freedman; Emy J Chen; Marsha A Moses; Susan Kilroy; Stefan Duensing; Christopher Fletcher; Jonathan A Fletcher; Lynn Hlatky; Philip Hahnfeldt; Judah Folkman; Arja Kaipainen Journal: J Clin Invest Date: 2002-10 Impact factor: 14.808