Significance of the biopharmaceutical properties of tramadol sustained-release formulations for chrono-pharmacologically optimized treatment of pain from various sources
A. Warnke1, B. Schug1, F. Vanderbist2, H. Blume1
1 SocraTec R&D GmbH, Oberursel, Germany, and 2 Laboratoires SMB SA, Brussels, Belgium
DOI 10.5414/CPP47405
Abstract
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 Cmax-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 AUC0-48-values) was calculated as 4,802.5 ng × h/ml after morning and 4,767.0 ng × 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.
Author Details
Authors
Departments
- 1 SocraTec R&D GmbH, Oberursel, Germany, and
- 2 Laboratoires SMB SA, Brussels, Belgium
Address
A. Warnke
SocraTec R&D GmbH
Feldbergstraße 27-29
61440 Oberursel, Germany
Email:
[email protected]
Citation
A. Warnke, B. Schug, F. Vanderbist and H. Blume.Significance of the biopharmaceutical properties of tramadol sustained-release formulations for chrono-pharmacologically optimized treatment of pain from various sources. 2009; 47: 405-412. doi: 10.5414/CPP47405.
