Significance of the biopharmaceutical properties of tramadol sustained-release formulations for chrono-pharmacologically optimized treatment of pain from various sources.

Author(s): Warnke A, Schug B, Vanderbist F, Erbist, Blume H

Affiliation(s): SocraTec R&D GmbH, Oberursel, Germany. andre.warnke@socratec-pharma.de

Publication date & source: 2009-06, Int J Clin Pharmacol Ther., 47(6):405-12.

Publication type: Comparative Study; Randomized Controlled Trial; Validation Studies

Tramadol is currently one of the most frequently used opioid analgesics in the world. OBJECTIVE: The objective of this study was to investigate the rate and extent of tramadol bioavailability following evening versus morning intake of an extended-release pellet system designed for once daily administration. Moreover, the suitability of the preparation for chrono-adjusted pharmacotherapy was to be investigated. METHODS: 18 male and female volunteers were enrolled in the study and treated with 200 mg tramadol extended-release capsules, which were to be taken in the fasted state between 7:30 and 8:00 a.m. or p.m., respectively. The parent compound and its O-desmethyl-metabolite were analyzed in plasma samples using a LC-MS/MS procedure. RESULTS: Maximum exposure of tramadol (geometric means of C(max)-values) was determined as 289.3 ng/ml after morning and 283.1 ng/ml after evening administration. Extent of tramadol exposure (geometric means of AUC(0-48)-values) was calculated as 4,802.5 ng x h/ml after morning and 4,767.0 ng x h/ml after evening administration. Also tmax-values were comparable after morning and evening administration (9.00 vs. 9.50 hours). Statistical analyses, based on conventional bioequivalence approach, revealed no evidence of any impact of the time-point of administration on the biopharmaceutical performance of the dosage form investigated here. CONCLUSIONS: Bioavailability of the extended-release tramadol capsules for once daily administration is not affected by the time-point of administration. Total and maximum exposure of the product was bioequivalent after intake in the morning and at night. Thus, the time-point of administration may be adjusted to the patient's needs without any significant change in the in-vivo performance.