Clozapine metabolism rate as a possible index of drug-induced granulocytopenia.
A possible relationship between haematological adverse reactions and clozapine (CLZ) metabolism rate was studied. Sixteen chronic schizophrenic outpatients (mean age 34.62 years +/- 7.56 SD) were treated with CLZ, 75-600 mg/daily for 9 weeks. CLZ and norclozapine (NCLZ) plasma levels were determined weekly, contemporarily with blood cell counts. CLZ plasma levels ranged from 25 to 1270 ng/ml (mean 266.27 ng/ml +/- 197.44 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)/l (mean 9.37 10(9)/l +/- 2.94 SD) and neutrophil count ranged from 1.8 to 13.4 10(9)/l (mean 5.73 +/- 2.57 SD). No correlation was found between CLZ dosage and NCLZ plasma levels. Both CLZ and NCLZ plasma levels correlated positively with neutrophil count (CLZ: P = 0.001, r = 0.26; 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, as an index of CLZ metabolism, might be a possible risk factor associated with CLZ treatment.
Department of Clinical Psychiatry, University of Milan, I.R.C.C.S. Ospedale Maggiore di Milano, Italy. maurimc@polic.cilea.it
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Mauri
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Rudelli
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Bravin
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Gianetti
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Giuliani
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Guerrini
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Orlandi
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Invernizzi
D000328:Adult; D000380:Agranulocytosis / Q000139:chemically induced* / Q000473:pathology*; D014150:Antipsychotic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003024:Clozapine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D007964:Leukocytosis / Q000139:chemically induced / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy / Q000473:pathology
D014150:Antipsychotic Agents; D003024:Clozapine