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

The effect of food on the oral pharmacokinetics of thalidomide and the relative bioavailability of two oral thalidomide formulations were determined in an open label, single dose, randomized, three‐way crossover study. Five male 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 conditions. The high‐fat meal resulted in a 0.5–1.5 h absorption lag time, an increased mean Cmax, a decreased mean AUC and a delay in mean Tmax. The Serral tablet formulation resulted in a lower mean Cmax, and slower terminal decline in plasma thalidomide concentrations compared with both Celgene treatments. Mean Cmax concentrations were 1.99±0.41 µg/mL (range 1.28–2.76) within 4.00±1.13 h (2–5) for the Celgene formulation fasted, 2.17±0.51 µg/mL (1.43–3.01) within 6.08±2.33 h (3–12) for the Celgene formulation with food, and 1.05±0.31 µg/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 formulation exhibited slightly greater bioavailability than Serral's formulation, with mean ratios of 122% and 110% for Ln‐transformed AUC0–t and AUC0–∞, respectively. The mean Cmax for the Celgene formulation was approximately two times greater than Serral's. Food delayed the onset of absorption 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 resulted in a two‐fold greater Cmax and 10% greater AUC0–∞ than the Serral formulation. Copyright © 2000 John Wiley & Sons, Ltd.