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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, age-related kinetic differences did not approach significance. |
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