Onset of analgesic effect and plasma levels of controlled-release tramadol (Tramadol Contramid once-a-day) 200-mg tablets in patients with acute low back pain.

BACKGROUND AND AIMS: Tramadol hydrochloride, a centrally acting, synthetic analgesic, has been available in Europe since 1977 in a variety of formulations and in the United States since 1995. Its clinical efficacy was established in a variety of painful conditions (cance rpain, neuropathic pain, and osteoarthritis). Nonetheless, little published data exist regarding the relationship between analgesic onset and minimum therapeutic plasma levels. Tramadol Contramid once-a-day (OAD) demonstrates a pharmacokinetic profile with a sharp initial absorption slope similar to the pharmacokinetic profile of the immediate-release tramadol, suggesting that both the immediate-release and the once-daily (Contramid) formulation may produce a similar onset of analgesia. METHODS: This multicentre, open-label, single-dose study examined the pharmacokinetics/pharmacodynamics of Tramadol Contramid OAD in patients with acute low back pain. Patients who signed informed consent were screened and washed-out of prior analgesics. Patients received one dose of Tramadol Contramid OAD 200 mg. The patients indicated the time of onset of pain relief (stopwatch method). Ratings of pain intensity and pain relief and pharmacokinetic samples were taken prior to dosing, at the onset of pain relief and 3 and 6 hours postdose. No rescue medication was permitted until the end of the study (6-hour postdose). Adverse events were monitored throughout the study. RESULTS: Forty of the 47 patients enrolled completed the study. Onset of perceptible pain relief was achieved within 1 hour for the majority of patients and at plasma levels, suggesting a therapeutic threshold between 50 and 100 ng/mL. Two patients did not experience any pain relief CONCLUSIONS: The results of this exploratory study suggest that similar to immediate-release tramadol, onset of analgesia for this controlled-release formulation of tramadol (Tramadol Contramid OAD) occurs within 1 hour at a mean therapeutic threshold concentration of 56 +/- 38 ng/mL.

A comparison of the analgesic efficacy of Tramadol Contramid OAD versus placebo in patients with pain due to osteoarthritis.

One thousand twenty-eight (1,028) patients with pain due to osteoarthritis (OA) of the knee were enrolled in this multicenter, randomized, double-blind, parallel study designed to assess the analgesic efficacy and safety of Tramadol Contramid OAD compared to placebo. An open-label phase was followed by a double-blind phase, in which a total of 646 patients were randomized to double-blind treatment with placebo or Tramadol Contramid OAD. Patients were titrated to their optimal dose (200mg or 300 mg), which was maintained for 12 weeks. An absolute mean reduction of 3.0+/-2.1 on a Pain Intensity Numerical Rating Scale (PI-NRS) was noted in the Tramadol Contramid OAD treatment group. The difference between active and placebo groups regarding this absolute mean reduction was statistically significant (P<0.001) throughout the study. The responder analysis demonstrated that a significantly greater percentage of patients in the active treatment arm achieved a reduction of >or=1 and >or=2 points on the PI-NRS score by the end of the study (P=0.035). A significantly greater percentage of respondents in the Tramadol Contramid OAD group indicated improvement on both the Patient and Physician Global Impressions of Change (P=0.0002). Both the 200mg and 300 mg doses contributed to the overall superiority of Tramadol Contramid OAD. The most frequent adverse events were consistent with the known side effects of tramadol and were generally mild to moderate in intensity. These results confirm that Tramadol Contramid OAD given once daily is an efficacious and safe treatment for pain due to OA.