The rate and extent of accumulation of clobazam and its major metabolite, desmethylclobazam, during multiple dosage with clobazam were evaluated in 4 similarly sized groups of young male, young female, elderly male, and elderly female volunteers. Subjects received single 10mg doses of clobazam daily for 22 consecutive days. Plasma levels were measured during and after the period of dosage. Compared with the young male subjects, elderly males had slower rates of clobazam accumulation and washout, higher steady-state plasma levels, and lower steady-state clearance. Accumulation of desmethylclobazam also was slower and more extensive in the elderly male group. Among females, however, agerelated kinetic differences did not approach significance.Among all subjects, pharmacokinetic variables for clobazam determined in a previous single-dose study were highly consistent with the multiple-dose pharmacokinetic profile. Single-dosevspost-multiple dosage half-life, single-dosevssteady-state clearance, observedvspredicted accumulation ratios, and observedvspredicted steady-state plasma concentrations were all highly correlated, with regression line slopes close to unity. Thus, reduced single-dose clearance of clobazam in elderly men leads to slower and more extensive accumulation during multiple dosage. The single-dose pharmacokinetic profile of clobazam is highly predictive of drug behaviour during repeated dosage, suggesting that clobazam kinetics are dose- and concentration-independent within the range studied, and that self-induction or inhibition of clearance is not evident during 3 weeks of dosage.