LAUSR

PurposeCombination 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.MethodsA 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 4 days in each period: pregabalin 150 mg twice daily; tramadol extended-release (ER) 200 mg in the morning, and 100 mg in the evening; and co-administration of pregabalin 150 mg and tramadol ER 200 mg in the morning, and pregabalin 150 mg and tramadol ER 100 mg in the evening.ResultsA 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.ConclusionsThere 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.