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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


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.


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

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van Tulder MW, Becker A, Bekkering T, et al.: European guidelines for the management of acute nonspecific low back pain in primary care. Eur Spine J. 2006; 15 Suppl 2: S169-S191.

World Health organization: Chronic Rheumatic Conditions. Geneva: WHO, 2007.

New South Wales Therapeutic Assessment Group: Prescribing Guidelines for Primary Care Clinicians, Low Back Pain: Rational use of Opioids in Chronic or Recurrent Non-Malignant Pain. New South Wales: NSW Therapeutic Assessment Group, 2002.

Patel AT, Ogle AA: Diagnosis and management of acute low back pain. Am Fam Physician. 2000; 61(6): 1779-1790.

Roth SH: Nonsteroidal anti-inflammatory drugs: Gastropathy, deaths, and medical practice. Ann Intern Med. 1988; 109(5): 353-354.

Roth SH, Bennett RE: Nonsteroidal anti-inflammatory drug gastropathy. Recognition and response. Arch Intern Med. 1987; 147(12): 2093-2100.

Griffin MR, Piper JM, Daugherty JR, et al.: Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons. Ann Intern Med. 1991; 114(4): 257-263.

Schafer AI: Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis. J Clin Pharmacol. 1995; 35(3): 209-219.

Raber M, Hofmann S, Momberger H, et al.: Analgesic efficacy and tolerability of tramadol 100mg sustained-release capsules in patients with moderate to severe chronic low back pain. Clin Drug Investig. 1999; 17(6): 415-423.

Schnitzer TJ, Gray WL, Paster RZ, et al.: Efficacy of tramadol in treatment of chronic low back pain. J Rheumatol. 2000; 27(3): 772-778.

Raffa RB, Friderichs E: The basic science aspect of tramadol hydrochloride. Pain Rev. 1996; 3(4): 249-271.

Reimann W, Schneider F: Induction of 5-hydroxytryptamine release by tramadol, fenfluramine and reserpine. Eur J Pharmacol. 1998; 349(2-3): 199-203.

Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004; 43(13): 879-923.

Grond S, Zech D, Lynch J, et al.: Tramadol–A weak opioid for relief of cancer pain. Pain Clin. 1992; 5(4): 241-247.

Harati Y, Gooch C, Swenson M, et al.: Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy. Neurology. 1998; 1(50): 1842-1846.

Sindrup SH, Andersen G, Madsen C, et al.: Tramadol relieves pain and allodynia in polyneuropathy: A randomised, doubleblind, controlled trial. Pain. 1999; 83(1): 85-90.

Jensen EM, Ginsberg F: Tramadol versus dextropropoxyphene in the treatment of osteoarthritis; A short-term double-blind study. Drug Invest. 1994; 8(4): 211-218.

Roth SH: Efficacy and safety of tramadol HCl in breakthrough musculoskeletal pain attributed to osteoarthritis. J Rheumatol. 1998; 25(7): 1358-1363.

Nossol S, Schwarzbold M, Stadler T: Treatment of pain with sustained-release tramadol, 100, 150, 200 mg: Results of a post-marketing surveillance study. Int J Clin Pract. 1998; 52(2): 115-121.

Mattia C, Coluzzi F: Once-daily tramadol in rheumatological pain. Expert Opin Pharmacother. 2006; 7(13): 1811-1823.

Malonne H, Sonet B, Streel B, et al.: Pharmacokinetic evaluation of a new oral sustained release dosage form of tramadol. Br J Clin Pharmacol. 2004; 57(3): 270-278.

Tiwari SB, Murthy TK, Pai MR, et al.: Controlled release formulation of tramadol hydrochloride using hydrophilic and hydrophobic matrix system. AAPS PharmSciTech. 2003; 4(3): E31.

Hair PI, Curran MP, Keam SJ: Tramadol extended-release tablets in moderate to moderately severe chronic pain in adults: Profile report. CNS Drugs. 2007; 21(3): 259-263.

Karhu D, Bouchard S: Pharmacokinetic evaluation of a novel one-a-day tramadol hydrochloride formulation, 34th Annual Meeting of the American College of Clinical Pharmacology. Rockville, MD, American College of Clinical Pharmacology, 2005.

Karhu D, Bouchard S: Comparative bioavailability of tramadol contramid once-a-day and tramadol immediate-release tablets, 23rd annual meeting of the American Academy of Pain Medicine (AAPM), New Orleans, LA, USA, 2007.

Lenaerts V, Moussa I, Dumoulin Y, et al.: Cross-linked high amylose starch for controlled release of drugs: Recent advances. J Control Release. 1998; 53(1-3): 225-234.

Medical Economics Company: PDR Physicians’ Desk Reference (60th edition). Montvale, NJ, USA: Thomson, 2006.

Hancock BC, Carlson GT, Ladipo DD, Langdon BA, Mullarney MP. The powder flow and compact mechanical properties of two recently developed matrix-forming polymers. J Pharm Pharmacol. 2001; 53(9): 1193-1199.

Lintz W, Barth H, Osterloh G, et al.: Bioavailability of enteral tramadol formulations. Drug Res. 1986; 36(2): 1278-1283.

Garrido MJ, Habre W, Rombout F, et al.: Population pharmacokinetic/pharmacodynamic modelling of the analgesic effects of tramadol in pediatrics. Pharm Res. 2006; 23(9): 2014-2023.

Bamigbade TA, Langford RM: The clinical use of tramadol hydrochloride. Pain Rev. 1998; 5: 155-182.

Lehmann K, Kratzenberg U, Schroeder-Bark B, et al.: Postoperative patient-controlled analgesia with tramadol: Analgesic efficacy and minimum effective concentrations. Clin J Pain. 1990; 6(3): 212-220.

Katz WA: Pharmacology and clinical experience with tramadol in osteoarthritis. Drugs. 1996; 52(3): 39-47.

Burch F, Fishman R, Messina N, et al.: A comparison of the analgesic efficacy of tramadol contramid OAD versus placebo in patients with pain due to osteoarthritis. J Pain Symptom Manage. 2007; 34(3): 328-339.

Fishman RL, Kistler CJ, Ellerbusch MT, et al.: Efficacy and safety of 12 weeks of osteoarthritic pain therapy with once-daily tramadol (Tramadol Contramid OAD). J Opioid Manag. 2007; 3(5): 273-280.



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