Clozapine, norclozapine plasma levels, their sum and ratio in 50 psychotic patients: influence of patient-related variables.

Abstract

Steady-state plasma concentrations of clozapine and norclozapine, its major metabolite, as well as their sum and ratio (norclozapine/clozapine), were evaluated in 50 in- and outpatients taking clozapine and naturalistically recruited. Drug plasma concentrations were measured by means of a reversed-phase high-performance liquid chromatography (RPLC) method with an ultraviolet detection. Daily doses (milligrams per kilogram of body weight) of clozapine correlated positively with clozapine plasma parameters, except with the norclozapine/clozapine ratio, in all patients. When the patients were divided in subgroups with respect to gender, the corresponding plasma concentrations were no longer dose-related in men. A lack of significant correlation was observed also in patients (n=23) co-treated with typical neuroleptics. Conversely, dose-concentration correlations were significant in either smoker or nonsmoker patients. No significant relationship between body weight and clozapine plasma parameters was reported. Further, we observed (1) a trend towards higher medians of clozapine or total analytes in women than those reported in men (P=.09 and .07); (2) no significant difference in plasma levels obtained in subjects younger than 34 years and subjects 34 years old or older; (3) a trend towards higher norclozapine and clozapine plus norclozapine levels (P=.05 and .08) in nonsmoker than smoker patients; (4) no significant difference between clozapine plasma parameters measured in patients co-medicated with typical neuroleptics and in patients receiving clozapine alone.

• Authors: Lionella Palego, Luciano Biondi, Gino Giannaccini, Nannina Sarno, Simona Elmi, Antonio Ciapparelli, Giovanni Battista Cassano, Antonio Lucacchini, Claudia Martini, Liliana Dell'Osso
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 26 Issue 3 Pg. 473-80 (Apr 2002) ISSN: 0278-5846 [Print] England
• PMID: 11999897 (Publication Type: Comparative Study, Journal Article)

Chemical References

• norclozapine
• Clozapine

Topics

• Adolescent
• Adult
• Aged
• Clozapine (analogs & derivatives, blood, therapeutic use)
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Female
• Humans
• Male
• Middle Aged
• Patients (statistics & numerical data)
• Psychotic Disorders (blood, drug therapy, psychology)
• Sex Factors
• Smoking (blood)
• Statistics, Nonparametric