Effect of a high-fat meal on thalidomide pharmacokinetics and the relativebioavailability of oral formulations in healthy men and women

The effect of food on the oral pharmacokinetics of thalidomide and the rela tive bioavailability of two oral thalidomide formulations were determined i n an open label, single dose, randomized, three-way crossover study. Five m ale and eight female healthy volunteers received a single oral dose of 200 mg Celgene thalidomide capsules under fasted and non-fasted conditions, and a single dose of 200 mg tablets of Serral thalidomide under fasted conditi ons. The high-fat meal resulted in a 0.5-1.5 h absorption lag time, an incr eased mean C-max, a decreased mean AUC and a delay in mean T-max. The Serra l tablet formulation resulted ina lower mean C-max, and slower terminal dec line in plasma thalidomide concentrations compared with both Celgene treatm ents. Mean C-max concentrations were 1.99 +/- 0.41 mug/mL (range 1.28-2.76) within 4.00 +/- 1.13 h (2-5) for the Celgene formulation fasted, 2.17 +/- 0.51 mug/mL (1.43-3.01) within 6.08 +/- 2.33 h (3-12) for the Celgene formu lation with food, and 1.05 +/- 0.31 mug/mL (0.62-1.65) within 6.23 +/- 1.88 h (5-10) for the Serral formulation fasted. Mean terminal half-lives were 13.50 +/- 6.77 h for the Serral product, compared with 5.80 +/- 1.72 h and 5.09 +/- 1.03 h for Celgene fasted and fed, respectively. Celgene's formula tion exhibited slightly greater bioavailability than Serral's formulation, with mean ratios of 122% and 110% for Ln-transformed AUC(0-t) and AUC(0-inf inity), respectively. The mean C-max for the Celgene formulation was approx imately two times greater than Serral's. Food delayed the onset of absorpti on of by 0.5-1.5 h, but had little effect on the extent of absorption from the Celgene capsule. Under fasted conditions, the Celgene thalidomide resul ted in a two-fold greater C-max and 10% greater AUC(0-infinity) than the Se rral formulation. Copyright (C) 2000 John Wiley & Sons, Ltd.