DARU Journal of Pharmaceutical Sciences17420151213Pharmacokinetic study of tramadol and its three metabolites in plasma, saliva and urine245255M.RRouiniYArdakani20151213Background and the purpose of the study: Pharmacokinetic parameters of tramadol and its three metabolites in plasma, saliva and urine following administration of 100 mg single oral dose were investigated in 24 healthy volunteers.Materials and Methods: 12 male and 12 female healthy volunteers received a single oral dose of tramadol and Plasma, mixed saliva -secreted samples without any stimulation and urine were analyzed for Tramadol and its main metabolites by HPLC method.Results and Disscusion: Almost 16.2% of tramadol and 11.2, 1.1 and 5.0% of O-desmethyltramadol (M1), N-desmethyltramadol (M2) and N,O-didesmethyltramadol (M5) respectively were recovered in 30 hrs collected urine. Renal clearance of tramadol, M1, M2 and M5 were 114.7 ± 44.5, 193.9 ± 67.6, 116.1 ± 61.8 and 252.0 ± 91.5 (mL/min) respectively. The maximum plasma concentration of tramadol, M1, M2 and M5 were 349.3 ± 76.7, 88.7±30.3, 23.1 ± 11.4 and 30.0 ± 11.7 (ng/mL) at 1.6 ± 0.4, 2.4 ± 0.7, 2.8 ± 1.0 and 2.7 ± 1.4 hrs after drug administration respectively. Tramadol and its metabolites appeared in a significant amount in saliva with the saliva/plasma ratios of 9.0, 1.6, 12.3 and 2.8 for tramadol, M1, M2 and M5 according to AUC(0-24) respectively. Conclusion: Conclusion Strong correlations were found between plasma and saliva concentrations for all studied compounds and a dissection to pre and post absorption components improved these correlations. Results o f this study suggests that saliva is a suitable alternative to plasma for clinical and toxicological studies of tramadol and in addition to passive diffusion, a possible active transport is also suggested to describe the elevated saliva/plasma ratios for these compounds.https://daru.tums.ac.ir/index.php/daru/article/view/552https://daru.tums.ac.ir/index.php/daru/article/download/552/441