Introduction:

The bioavailability of Tramadol Contramid^® OAD and Tramadol immediate-release (IR) (Ultram^®) was compared following single-dose administration and at steady state in two separate studies.

Methods:

Both studies had open-label, randomized, 2-way crossover designs. The protocols were approved by an ethics committee, and written informed consent was obtained from each subject prior to study start. Twenty-six healthy adult subjects were enrolled in each study. All subjects completed the steady-state study, and 24 subjects completed the single-dose study. In both studies, Tramadol Contramid^® OAD was administered orally as a 200-mg tablet dose once daily, and Tramadol IR was administered as one 50-mg tablet QID. In the steady-state study, each treatment was administered for five consecutive days. Plasma tramadol and O-desmethyltramadol levels were determined using a validated LC/MS/MS method. Primary pharmacokinetic parameters [single-dose: AUC_0-t, AUC_0-inf and C_max; steady-state: AUC_0-24 and C_max] were assessed by ANOVA.

Results:

 In both studies, the AUC parameters met bioequivalence criteria (90% CI within 80-125%) and the C_max of Tramadol Contramid^® OAD was lower than that of Tramadol IR. Following single-dose administration, the mean tramadol concentrations at 1 hour post dose were within the therapeutic range (100-300 ng/mL): 110 ± 40 ng/mL for Tramadol Contramid^® OAD and 158 ± 54 ng/mL for Tramadol IR. Steady-state concentrations were attained within 48 hours following the first dose of Tramadol Contramid^® OAD. Peak-to-trough variation was 77% for Tramadol Contramid^® OAD, compared with 91% for Tramadol IR.

Conclusion:

Tramadol Contramid^® OAD 200 mg achieves therapeutic plasma concentrations within 1 hour of administering the first dose and maintains these for 24 hours; exposure is equivalent to Tramadol IR 50 mg QID with respect to AUC, with a lower C_max.