EFFECT OF AGE ON THE PHARMACOKINETICS OF DIAZEPAM GIVEN IN CONJUNCTION WITH SPINAL-ANESTHESIA

There was a significant positive correlation between age and elimination-phase half-life (t( 1/2 β); P<0.05), age and total drug plasma clearance (Cl(tot); P<0.05), and age and the volume of distribution at steady state (V(dss); P<0.05). Similarly, the elimination half-life (t( 1/2 β)) and total plasma clearance (Cl(tot); P<0.001) correlated. No correlation was found between the age and distribution phase half-life (α-phase, t( 1/2 α); P<0.10), age and central distribution volume (V(dc); P<0.10) age and distribution ratio (k12/k21; P<0.10), and age and the elimination rate constant (k(el); P<0.10). The pharmacokinetic mean (±SD) data from the 14 patients are shown. Of the three main metabolites of diazepam, N-demethyldiazepam, N-methyloxazepam, and oxazepam, only N-demethyldiazepam was detectable in all plasmas, at low levels. No correlation between age and the plasma levels of this major metabolite of diazepam was found. In plasmas of younger patients N-desmethyldiazepam was first detected after 30 min to one hour. Thereafter it increased to reach a maximum between 24 and 48 hours, and then decreased until 72 hours. In the elderly, N-demethyldiazepam was detected later (after two to six hours), and peak concentrations were lower, but occurred generally at the same time or only a little later than in younger subjects. The mean (±SEM) values of N-demethyldiazepam in the plasmas of patients less than and more than 60 years of age are shown.