A NATURALISTIC STUDY OF CLOZAPINE SERUM CONCENTRATIONS IN PSYCHIATRIC-PATIENTS

The serum clozapine concentration (S-Cloza) was measured for the first time in 213 patients referred to routine therapeutic drug monitoring (TDM). Blood samples for determination of S-Cloza were drawn during st eady state in the morning about 12 h after the evening dose. The S-Clo za and daily dose (median with interquartile range in parentheses) wer e 960 (553-1662) nmol/l and 350 (238-425) mg, respectively. The S-Cloz a was positively correlated to the daily dose (P<0.01), but only 29% o f the interindividual variation of S-Cloza was explained by dose. The median ratio of S-Cloza to dose (C/D) was 23% higher in females than i n males (P<0.01), and the ratio was only slightly influenced by age. F orty-five per cent of the patients received clozapine as the only neur oleptic drug, and 39% were receiving concomitant treatment with conven tional neuroleptics, but no difference between median S-Cloza or media n dose of the two groups was found. An S-Cloza of 1285 nmol/l has been suggested by others as the lower threshold for predicting response to treatment. An S-Cloza above this level was found in only 34.4% of the patients. A therapeutic range for S-Cloza has not been established, b ut to recognize unusually low or high concentrations, it may be useful to know that 80% of the patients had S-Cloza within a range of 300-20 00 nmol/l.