The Effect of Single-Dose Tramadol on Oxycodone Clearance

We have noticed increased prescribing of tramadol by emergency physicians for breakthrough pain in patients chronically taking oxycodone. Both oxycodone and tramadol undergo oxidative metabolism by CYP2D6 and CYP3A4, suggesting the possibility that tramadol may compete with oxycodone for metabolism. A randomized controlled trial in 10 human volunteers was performed to determine if single-dose tramadol therapy would impair oxycodone clearance. Subjects were randomized whether to enter the control or experimental arm of the study first, with each subject serving as his or her own control. In the control arm, each subject received 10 mg immediate-release oxycodone orally and had serial plasma oxycodone and oxymorphone concentrations measured over 8 h. The experimental arm was identical except that 100 mg tramadol was ingested 1.5 h before oxycodone. Clearance divided by fraction absorbed (CL/f) was calculated using the dose and the area under the 8-h time-plasma oxycodone concentration curve. Peak plasma oxycodone concentrations (Cmax) and time until peak oxycodone concentrations (Tmax) were secondary outcome parameters. Group size was chosen to produce a power of 0.8 to detect a 20% difference in CL/f between study arms. Values for CL/f, Cmax, and Tmax were compared between study arms using two-tailed, paired t-tests. No statistically significant difference between groups was demonstrated for any parameter. We failed to demonstrate that single doses of tramadol impaired oxycodone clearance.