Effect of food and tablet age on relative bioavailability and pharmacodynamics of two tolbutamide products.

Relative bioavailability and pharmacodynamics of tolbutamide from two different commercially available tablet products have been evaluated in healthy subjects in a single-dose crossover study. "Fresh" tablets and tablets aged by exposure to 98% relative humidity for 3 d at ambient temperature were studied. Aging was found to differentially affect both the rate and extent of absorption for the two products. Differences were reflected by log AUC (generic product AUC 10% lower than the product of the innovator, p = 0.047), peak concentration (generic product 27% lower than the product of the innovator, p = 0.0001), mean absorption time (generic product 119% longer than the product of the innovator, p = 0.0008), and mean residence time (generic product 17% longer than the product of the innovator, p = 0.011). Aged product from the innovator produced statistically significantly higher serum tolbutamide concentrations for the first 8 h postdose and a greater glucose depression than aged generic product. Administration of unaged tablets with food produced differences in the rate of absorption, manifested in time-to-peak (generic product 69% later than the product of the innovator, p = 0.006), peak concentration (generic product 18% lower than the product of the innovator, p = 0.001), and mean absorption time (generic product 104% greater than the product of the innovator, p = 0.007), which resulted in statistically significantly higher tolbutamide concentrations for the product of the innovator than for the generic product for the first 3 h postdose.(ABSTRACT TRUNCATED AT 250 WORDS)

RCT Entities:   Population Interventions Outcomes