CSF and serum concentrations of clozapine and its demethyl metabolite: a pilot study

With the aim of exploring putative correlations between serum and CSF levels of clozapine and its demethyl metabolite, lumbar puncture was performed on four male and five female schizophrenic patients during long-term treatment with clozapine. Three consecutive 6-ml fractions were collected after at least 8 h of bedrest and fasting. On comparing serum and CSF levels, a correlation was found for norclozapine in the third (13-18 ml) CSF fraction. Norclozapine in the first (0-6 ml) CSF correlated significantly with height. The CSF/serum ratio of clozapine in the first fraction was correlated significantly with body weight. No correlations were found between serum levels of clozapine and norclozapine, or between the serum and CSF levels of clozapine. The study suffers from a small number of patients (for ethical reasons), but the present results might be explicable if the first (0-6 ml) CSF fraction represents a cul-du-sac of the CSF, mirroring the previous day's drug levels. The second fraction, then, will represent the CSF level in the steady state during the night.