Clonazepam and 7-aminoclonazepam in human plasma.

The purpose of our study was to evaluate the hypothesis that much of the reported variability in the range of concentrations of plasma clonazepam (and also in the range of concentrations of its major metabolite, 7-aminoclonazepam) encountered in pediatric epilepsy patients is due to collection of samples at random times after dosing. High-performance liquid chromatographic analyses were performed on routinely ordered blood samples collected from chronically dosed outpatients during regular clinic visits. Thirty-six samples from 26 different children (age 0.25-19.6 years, mean 6.3 years) were analyzed. Specific dosing and sample collection times were obtained at the time of blood collection; demographic data were obtained from the clinic charts. A portion of the variation for both clonazepam and its major metabolite was accounted for by differences in daily dosage used. However, by accurate recording of dosage, administration times, and sample collection time, we graphically demonstrated that the majority of the variations in measured clonazepam and 7-aminoclonazepam concentrations was due to the time elapsed between the last dose and the time of sample collection. Thus, random sample collection times (especially during the drug distribution phase and following frequent dosing) may account, in part, for the poor correlation between plasma concentrations and reported anticonvulsant or toxic effects.