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Single‐Dose Oral Pharmacokinetics of Three Formulations of Thalidomide in Healthy Male Volunteers
Author(s) -
Teo Steve K.,
Colburn Wayne A.,
Thomas Steve D.
Publication year - 1999
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127009903901108
Subject(s) - cmax , pharmacokinetics , bioequivalence , pharmacology , thalidomide , medicine , crossover study , absorption (acoustics) , chemistry , materials science , alternative medicine , pathology , composite material , multiple myeloma , placebo
Thalidomide was recently approved in the United States for the treatment of erythema nodosum leprosum, a complication of leprosy. The present study determined the bioequivalence and pharmacokinetics of Celgene's commercial and clinical trial thalidomide formulations and the Brazilian Tortuga formulation in an open‐label, single‐dose, three‐way crossover design. Seventeen healthy subjects were given 200 mg of thalidomide on three occasions, and blood samples were collected over 48 hours. Pharmacokinetic parameters were determined using compartmental methods for the two Celgene formulations and using noncompartmental methods for all three formulations. All subjects reported adverse events, none of which was serious or unexpected. Celgene formulations were bioequivalent when comparing C max , t max , and AUC. There was significant variability in plasma levels from the Tortuga formulation, giving a mean profile that was distinctly different from the two Celgene formulations with a lower C max value and a longer terminal phase. The lower C max was probably due to slower absorption. The terminal rate constant for the Tortuga formulation was significantly less, giving rise to a terminal half‐life of 15 hours compared to about 5 to 6 hours for the Celgene formulations. Confidence intervals for C max between the Tortuga and the Celgene formulations were outside the 80% to 125% range, indicating a lack of bioequivalence. Extent of absorption, as measured by AUC 0‐∞; , was approximately equal for all three formulations. Terminal half‐life for Tortuga was two to three times longer compared to the Celgene formulations and is clear evidence for absorption rate limitations. The two Celgene formulations showed similar pharmacokinetic parameters with profiles that were best described by a one‐compartment model with first‐order absorption and elimination. The authors conclude that Celgene's clinical trial and commercial thalidomide formulations are similar to each other and distinctly different from the Tortuga formulation and that all three formulations exhibited absorption rate—limited elimination .