Pharmacokinetics of Tramadol and O-Desmethyltramadol Enantiomers Following Administration of Extended-Release Tablets to Elderly and Young Subjects

Background Tramadol is frequently used in geriatric patients; however, pharmacokinetic (PK) publications on tramadol and O-desmethyltramadol (ODM) in elderly patients are rare. Objective Our objective was to characterize the PK of tramadol and ODM, including absorption processes and covariates for tramadol, in elderly and young subjects after single-dose administration of 200-mg extended-release tablets. Methods We conducted a PK study in 15 elderly (aged >= 75 years) subjects with mild renal insufficiency and 20 young (18-40 years) subjects; blood and urine samples were collected for 48 h post-dose. Non-compartmental analysis (NCA) of each tramadol and ODM enantiomer included area under the concentration-time curve (AUC), terminal elimination rate (k(el)), total body clearance, volume of distribution (V-area/F), and renal clearance (Clr(0-48)). A one-compartment population model of total tramadol concentration was parameterized with clearance (CL/F), volume of distribution (V/F), and mixed order absorption (first-order and zero-order absorption rate constants with lag times). Results NCA demonstrated comparable maximum plasma concentration (C-max) and AUC between age groups for tramadol enantiomers, but significant differences in V-area/F (mean 34 % higher) and kel (mean 28 % lower) in the elderly. PK of ODM were significantly different in the elderly for AUC(0-inf) (mean 35 % higher), Clr(0-48) (mean 29 % lower), and kel (mean 33 % lower). The population analysis identified age as a covariate of V/F (young 305 L; elderly 426 L), with a 50 % longer mean elimination half-life in the elderly. No differences in absorption processes were observed. Conclusions Tramadol exposure was similar between the age groups; exposure to ODM was higher in elderly subjects.