Plasma diazepam concentrations following prolonged administration

Abstract

Plasma diazepam and N-desmethyl diazepam concentrations were measured in patients receiving diazepam 5 mg or 10 mg i.v. at 4-h intervals for periods of 6-22 days. At both doses there was an accumulation of both diazepam and its metabolite, the latter reaching concentrations of up to two to three times that of the parent drug. Plasma diazepam concentrations reached a plateau after 8 days while the concentration of N-desmethyl metabolite continued to increase throughtout the period of drug administration. On discontinuation of diazepam therapy both diazepam and N-desmethyl diazepam concentrations decreased slowly, the former with a half-life of 2-4 days and the latter with a half-life of 4-8 days.