THE EFFECT OF AGE ON THE PHARMACOKINETICS OF THE OPIOID ANTAGONIST NALMEFENE

1 The disposition of nalmefene was evaluated in young and elderly norm al healthy volunteers. Subjects received either a single 1 mg (M = 18 young; n = 11 elderly) or 2 mg (n = 8 young; n = 15 elderly) intraveno us bolus dose of nalmefene. 2 Following the administration of nalmefen e, the initial plasma concentrations were significantly higher in elde rly vs young subjects. The higher concentrations were the result of th e 30 to 40% smaller central compartment apparent volume of distributio n that was observed in the elderly subjects as compared with the young volunteers (2.8 +/- 1.1 vs 3.9 +/- 1.1 1 kg(-1) for 1 mg dose). The e lderly volunteers also had a significantly shorter distributional half -life (t(1/2 lambda 1)) than young volunteers (0.7 +/- 0.7 vs 1.3 +/- 0.8 h for 1 mg dose). No significant differences between groups were o bserved for the elimination half-life, clearance or steady-state appar ent volume of distribution. 3 Although transiently higher nalmefene pl asma concentrations were observed in the elderly immediately following drug administration, there was no association between this observatio n and adverse events. We conclude that no dosage alteration is warrant ed in elderly patients.