Radioimmunoassay for 7-hydroxy metabolite of fluphenazine and its application to plasma level monitoring in schizophrenic patients treated long term with oral and depot fluphenazine.
Immunization of New Zealand white rabbits with a bovine serum albumin conjugate of 7-hydroxy-N-carboxyethyl-N-deshydroxyethylfluphenazine produced highly specific antisera for 7-hydroxyfluphenazine (7-OHFLU). A radioimmunoassay (RIA) was developed using antisera from one of the rabbits that enabled for the first time the determination of plasma levels of 7-OHFLU, an active metabolite of fluphenazine (FLU), in patients treated with oral FLU dihydrochloride or i.m. FLU decanoate. The assay method provided sufficient sensitivity to determine accurately 20 pg of 7-OHFLU in 200 microliters (0.1 ng/ml) of plasma with a coefficient of variation of < 10%. The antiserum used in the RIA for 7-OHFLU demonstrated negligible cross-reactivity with FLU and its metabolites such as FLU sulfoxide, N-deshydroxyethylFLU, FLU N4'-oxide, N-deshydroxyethyl-7-OHFLU, and 7-O-glucuronide of FLU and also with other antipsychotic agents and commonly coadministered drugs. The 7-OHFLU was present in measurable amounts in all plasma samples obtained at 4-week intervals from patients receiving a daily oral dose of 5 (n = 10), 10 (n = 13), or 20 (n = 14) mg of FLU dihydrochloride. Large interindividual variations in the plasma level of FLU and 7-OHFLU were noted and the mean plasma levels ratios of 7-OHFLU/FLU at these doses were 2.07 +/- 1.08, 2.07 +/- 1.13, and 2.02 +/- 0.82, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Aravagiri
M
M
Psychopharmacology Unit, University of California at Los Angeles.
Marder
S R
SR
Van Putten
T
T
Hawes
E M
EM
McKay
G
G
Midha
K K
KK
D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D016903:Drug Monitoring; D005476:Fluphenazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D007273:Injections, Intramuscular; D011817:Rabbits; D011863:Radioimmunoassay; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy
D003692:Delayed-Action Preparations; C086815:7-hydroxyfluphenazine; D005476:Fluphenazine