Whole saliva and plasma levels of clozapine and desmethylclozapine

Background: Therapeutic drug monitoring of clozapine as an aid in the treatment of schizophrenic states is commonly used in our hospital. Objective: Development of a high-performance liquid chromatographic method for the determination of clozapine (CLZ) and its major metabolite desmethylclozapine (DMCLZ) in plasma and saliva, and investigation of the relationship between plasma concentrations of CLZ and DMCLZ and concentrations in saliva in patients treated with clozapine. Methods: Subjects were either inpatients or outpatients with a DSM IV diagnosis of schizophrenia (n=34). Determination of CLZ and DMCLZ saliva concentrations appeared to be a satisfactory method to check compliance to treatment, particularly in outpatients. Results: Mean CLZ and DMCLZ plasma concentrations were 432+/-264 ng/ml (+/-SD) (range 90-1310 ng/ml) and 257+/-144 ng/ml (range 55-580 ng/ml) respectively. The CLZ/DMCLZ plasma ratio was equal to 1.7+/-0.5 (daily dosage 7.2+/-2.3 mg/kg, n=34). Mean CLZ plasma and saliva levels were 336+/-157 ng/ml (range 90-580 ng/ml) and 159+/-86 ng/ml (range 40-364 ng/ml), respectively (r=0.56, n=14). Mean DMCLZ plasma and saliva levels were 196+/-112 ng/ml (range 55-481 ng/ml) and 109+/-67 ng/ml (range 40-250 ng/ml), respectively (r=0.73, n=14). Mean CLZ/DMCLZ ratios determined in plasma and saliva were 1.9+/-0.6 (range 1.0-3.4) and 1.7+/-0.6 (range 1.0-3.2) respectively (r=0.85, n=14). CLZ and DMCLZ saliva concentrations appear to be useful for checking compliance to treatment, in particular among outpatients.