A pharmacokinetic drug-drug interaction study between pregabalin and tramadol in healthy volunteers.

Abstract

Combination therapy of pregabalin and tramadol is used to treat chronic neuropathic pain; however, the pharmacokinetic (PK) interactions of these drugs has not been studied. This study aimed to evaluate PK interactions between pregabalin and tramadol and the safety of combination therapy. A randomized, open-label, multiple-dose, three-treatment, three-period, six-sequence cross-over study was conducted in healthy subjects. All subjects received the following three treatments for 4days in each period: pregabalin 150mg twice daily; tramadol extended-release (ER) 200mg in the morning, and 100mg in the evening; and co-administration of pregabalin 150mg and tramadol ER 200mg in the morning, and pregabalin 150mg and tramadol ER 100mg in the evening. A total of 21 subjects completed the study with no clinically significant safety issues. For pregabalin, the geometric mean ratio (GMR) (90% CI; confidence interval) of combination therapy to monotherapy for maximum concentration at steady state (Cmax,ss) and area under the concentration curve from 0 to dosing interval time at steady state (AUCτ,ss) were 0.8801 (0.8043-0.9632) and 1.0830 (1.0569-1.1098), respectively. The corresponding values for tramadol were 1.0177 (0.9839-1.0526) and 1.0152 (0.9896-1.0414), respectively. The GMR (90% CI) of combination therapy to monotherapy of O-desmethyl-tramadol for Cmax,ss and AUCτ,ss was 1.0465 (1.0095-1.0848) and 1.0361 (1.0001-1.0734), respectively. There were no significant drug interactions between pregabalin and tramadol, considering that all of the 90% CI of PK measures were within the conventional bioequivalence range. Both drugs were well tolerated when administered concomitantly.