Clozapine, norclozapine plasma levels, their sum and ratio in 50 psychotic patients: influence of patient-related variables.
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.
Palego
Lionella
L
Department of Psychiatry, University of Pisa, Italy. liopal@yahoo.com
Biondi
Luciano
L
Giannaccini
Gino
G
Sarno
Nannina
N
Elmi
Simona
S
Ciapparelli
Antonio
A
Cassano
Giovanni Battista
GB
Lucacchini
Antonio
A
Martini
Claudia
C
Dell'Osso
Liliana
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D003024:Clozapine / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010361:Patients / Q000706:statistics & numerical data; D011618:Psychotic Disorders / Q000097:blood* / Q000188:drug therapy / Q000523:psychology; D012737:Sex Factors; D012907:Smoking / Q000097:blood; D018709:Statistics, Nonparametric
C058272:norclozapine; D003024:Clozapine