Determination of clozapine in serum by radioreceptor assay versus high-performance liquid chromatography: possible detection of hydroxy-metabolites.
Clozapine is an antipsychotic drug with few extra-pyramidal motor side-effects, used to treat schizophrenia which is resistant to classical neuroleptic therapy. This report shows that norclozapine but not clozapine-N-oxide has the same D2 receptor affinity as clozapine. Assay results suggest a bimodal distribution which may be explained by CYP1A2 polymorphism. Extensive metabolizers could produce other active metabolites, probably other hydroxy-clozapine derivatives.
Odou
P
P
Laboratoire de Pharmacie Clinique, Pharmacocinétique et de Pharmacologie Faculté des Sciences Pharmaceutiques et Biologiques, Lille, France.
Frimat
B
B
Fontaine
B
B
Luyckx
M
M
Brunet
C
C
Robert
H
H
Dine
T
T
Gressier
B
B
Cazin
M
M
Cazin
J C
JC
D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D003024:Clozapine / Q000031:analogs & derivatives / Q000097:blood* / Q000627:therapeutic use; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D006801:Humans; D006900:Hydroxylation; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; C058272:norclozapine; D003024:Clozapine; C079149:clozapine N-oxide