Sibutramine pharmacokinetics in young and elderly healthy subjects

Objective: To investigate the pharmacokinetics of the pharmacologically act ive metabolites of sibutramine (metabolites 1 and 2) in healthy young and e lderly volunteers following a single oral dose of sibutramine. Methods: This was an open, parallel-group study completed by 12 young (six male, six female; mean age 24.0 years) and 12 elderly (six male, six female , mean age 70.3 years) healthy volunteers. Blood samples were taken at inte rvals up to 48 h post-dose. Plasma concentrations of metabolites were deter mined using HPLC-MS. Model-independent pharmacokinetic parameters of the tw o metabolites were compared for the two age groups. Results: The similarity of the plasma profiles of the two desmethyl metabol ites showed that despite the possibility of reduced hepatic function due to age, the rate and extent of formation of these was the same in both young and elderly, i.e. sibutramine metabolism was not impaired in elderly subjec ts. There were also no significant differences in elimination of metabolite 2 between groups, although the elderly group showed a slight trend for a r eduction in k(el). Conclusions: The pharmacokinetics of the two pharmacologically active metab olites of sibutramine (metabolites 1 and 2) were not significantly differen t between the young and elderly groups in this study. Based on this informa tion, a similar dosing regimen would be appropriate for both the young and elderly.