Comparative bioavailability between two Tramadol once-daily oral formulations.
The aim of this study was to compare the pharmacokinetic profile and oral bioavailability of Tramadol Contramid once-daily (o.d.) 200 mg tablets (Labopharm, Canada) with that of Zytram 200 mg tablets (Zambon, Spain), following single-dose administration in 26 healthy volunteers. The study had an open, randomized, crossover design with a 7-day wash-out. Data from 24 subjects were used for the pharmacokinetic (PK) analysis. Racemic tramadol and racemic O-demethyltramadol (M1) were assayed in plasma using a liquid chromatography/tandem mass spectrometry method. Primary PK parameters estimated were AUC(0-t), AUC(0-infinity), C(max), C(24 h), and T(max). Results were compared using an ANOVA, and the residual variability thereby obtained was used to construct the classical 90% confidence intervals. The parametric Schuirmann's test was also performed. T(max) was analyzed by a nonparametric approach. For both racemic tramadol and racemic O-demethyltramadol, the ANOVA showed a statistically significant formulation effect. Significantly higher values were obtained for Tramadol Contramid o.d. for all PK parameters, except for T(1/2). For Tramadol Contramid o.d., mean tramadol plasma levels were maintained at a plateau level above 200 ng/ml from 4 to 16 h after dose, while for the reference formulation, that level was sustained from 4 to only 6 h. Consistent results for both formulations were obtained for the metabolite. At the end of the dosing interval, plasma tramadol and O-demethyltramadol concentrations were 39% and 49% higher, respectively, for Tramadol Contramid o.d. than those for Zytram (p < 0.0001). Tramadol Contramid o.d. could be considered suprabioavailable to Zytram o.d.
Hernandez-Lopez
C
C
Clinical Research Department, ESTEVE, Mare de Deu de Montserrat, Barcelona, Spain. chernandez@esteve.es
Martinez-Farnos
L
L
Karhu
D
D
Perez-Campos
T
T
Rovira
S
S
Encina
G
G
D000284:Administration, Oral; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001711:Biotransformation; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D013810:Therapeutic Equivalency; D014147:Tramadol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; C080580:O-demethyltramadol; D014147:Tramadol