Diazepam metabolism in normal man

Abstract

Diazepam given orally over a period of days produces cumulation in the serum of diazepam as well as N‐desmethyldiazepam. A balanced serum level is achieved at the end of the first week for diazepam, at the beginning of the second week for N‐desmethyldiazepam, and from this time on it is higher than the mother substance. The biologic half‐life of diazepam was found to be 54 hours, and the apparent biologic half‐life of N‐desmethyldiazepam, 92 hours. There was close correspondence between the serum levels of diazepam and its clinical effects. During continued administration over one to two weeks, some development of tolerance could be demonstrated. Cumulation of the metabolite was marked during continuous oral administration of diazepam, but clinical effects of the metabolite could not be demonstrated; effects seem to be related solely to serum levels of diazepam.