CLOZAPINE METABOLISM RATE AS A POSSIBLE INDEX OF DRUG-INDUCED GRANULOCYTOPENIA

A possible relationship between haematological adverse reactions and c lozapine (CLZ) metabolism rate was studied. Sixteen chronic schizophre nic outpatients (mean age 34.62 years +/- 7.56 SD) were treated with C LZ, 75-600 mg/daily for 9 weeks. CLZ and nor-clozapine (NCLZ) plasma l evels were determined weekly, contemporarily with blood cell counts. C LZ plasma levels ranged from 25 to 1270 ng/ml (mean 266.27 ng/ml +/- 1 97.44 SD), while NCLZ plasma levels ranged from 25 to 1280 ng/ml (mean 169.0 ng/ml +/- 127.94 SD). NCLZ/CLZ ratio ranged from 0.13 to 1.72 ( mean 0.72 +/- 0.28 SD). Leukocyte count ranged from 5.2 to 18.8 10(9)/ 1 (mean 9.37 10(9)/1 +/- 2.94 SD) and neutrophil count ranged from 1.8 to 13.4 10(9)/1 (mean 5.73 +/- 2.57 SD). No correlation was found bet ween CLZ dosage and NCLZ plasma levels. Both CLZ and NCLZ plasma level s correlated positively with neutrophil count (CLZ: P = 0.001, r = 0.2 6; NCLZ: P = 0.01, r = 0.20). The correlation between NCLZ/CLZ plasma level ratio and neutrophil count was significantly negative (P = 0.002 , r = 0.25). These preliminary data suggest that the NCLZ/CLZ ratio, a s an index of CLZ metabolism, might be a possible risk factor associat ed with CLZ treatment.