FLUMAZENIL KINETICS IN THE ELDERLY

In an open design, randomised, two-way cross-over study, a single 2 mg i. v. dose and, a single 30 mg oral dose of flumazenil were each admi nistered to a group of healthy young (n = 6) and elderly (n = 12) volu nteers (male: female 2/1). Plasma samples were collected at intervals and intact drug was assayed. Both the IV and oral doses of flumazenil were very well tolerated by both age groups and no severe or unexpecte d adverse effects were observed. The main complaints were dizziness an d headache, mainly after oral dosing, probably due to the higher C(max ) and AUC following this route of administration. After 2 mg i. v. the disposition parameters in the two age groups (elderly/young) were ver y similar: volume of distribution (V(ss)): 0.88/0.90 l.kg-1; total bod y clearance (Cl(PL)): 0.86/0.99 l.min-1, terminal elimination half-lif e (t1/2beta): 1.02/0.91 h. After the 30 mg oral dose the mean C(max) o f 87.6 ng.ml-1 (elderly) and 78.4 ng.ml-1 (young) were generally reach ed within 0.5 to 1 h. In 26% (elderly) and 23% (young), the absolute b ioavailability of flumazenil was very similar. It is concluded that th e absorption and disposition paramters of flumazenil were not signific antly affected by aging.