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

Adrian Sarbu, MD; Florin Radulescu, MD; Sybil Robertson, BScN; Sylvie Bouchard, MD, PhD

doi:10.5055/jom.2008.0032

Authors

Adrian Sarbu, MD
Florin Radulescu, MD
Sybil Robertson, BScN
Sylvie Bouchard, MD, PhD

DOI:

https://doi.org/10.5055/jom.2008.0032

Keywords:

acute, low back pain, tramadol, oncedaily, onset, clinical trial, pain relief, pharmacokinetic

Abstract

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 (cancer pain, 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 immediaterelease 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.

Author Biographies

Adrian Sarbu, MD

Centrul Medical SANA, Bucharest, Romania.

Florin Radulescu, MD

Centrul de Boli Rumatismale “Dr Ion Stoia” Policlinica CCBR SRL, Bucharest, Romania.

Sybil Robertson, BScN

Labopharm Inc, Laval, Québec, Canada.

Sylvie Bouchard, MD, PhD

Labopharm Inc, Laval, Québec, Canada.

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