Development and Application of a Radioimmunoassay for Fluphenazine Based on Monoclonal Antibodies and Its Comparison with Alternate Assay Methods

McKay, G.; Steeves, Taylor A.; Cooper, J.K.; Hawes, E. M.; Midha, K. K.

doi:10.1002/jps.2600790313

“…Plasma levels of fluphenazine were measured using a radioimmunoassay (RIA) which was validated for specificity using gas chromatography mass spectroscopy (Midha et al 1980;McKay et al 1990). The sensitivity of the assay was 0.1 ng/ml and the coefficient of variation was 3%.…”

Section: Assay Techniquesmentioning

confidence: 99%

Fluphenazine levels during maintenance treatment of recent-onset schizophrenia: relation to side effects, psychosocial function and depression

Gitlin

¹

,

Nuechterlein

²

,

Mintz

³

et al. 2000

View full text Add to dashboard Cite

show abstract

“…The antibodies used in the RIAs of FLU-SO, 7-OH-FLU, and FLU-NO were polyclonal antibodies raised against suitable trifluoperazine sulfoxide, trifluoperazine 7-hydroxy, and prochlorperazine N 4 '-oxide hapten-BSA conjugate based immunogens in New Zealand white rabbits (Aravagiri et al 1984(Aravagiri et al , 1985(Aravagiri et al , 1986 The antibody used in the RIA of FLU was monoclonal and raised against a FLU hapten-thyroglobulin-based immunogen using hybridoma technique in mice as reported previously (McKay et al 1990).…”

Section: Antibodiesmentioning

confidence: 99%

Distribution of Fluphenazine and Its Metabolites in Brain Regions and Other Tissues of the Rat

Aravagiri

¹

,

Marder

²

,

Yuwiler

³

et al. 1995

Neuropsychopharmacology

View full text Add to dashboard Cite

Rats were given 5, 10, or 20 mg/kg oral doses of fluphenazine (FLU) dihydrochloride daily for 15 days. FLU and its sulfoxide (FL-SO), 7-hydroxy (7-OH-FLU) and N4'-oxide (FLU-NO) metabolites were assayed in plasma, liver, kidney, fat, whole brain, and brain regions by specific and sensitive radioimmunoassays (RIA). All metabolites were detected in tissues at higher levels than in plasma, and the levels increased with dose. FLU was 10- to 27-fold higher in brain regions than in plasma. Brain vs plasma levels of FLU correlated more closely than levels of its metabolites. Liver contained the highest levels of all analytes at all doses. FLU-SO was the major metabolite in brain regions (24% to 96% of FLU) and accumulated in fat 43 to 75 times more than FLU. Levels of 7-OH-FLU and FLU-NO were very low in brain (1% to 20% of FLU). FLU-SO and FLU-NO had only 1% to 3% the affinity for D1 and D2 receptors, but 7-OH-FLU had 20% the D2 and 5% the D1 affinity of FLU. The low affinity for dopamine receptors and low brain-levels of metabolites of FLU indicate that they are not likely to contribute importantly to pharmacologic responses of FLU. Also, the estimated relative "activity factor" for these compounds in the brain indicated that the contribution to neuropharmacologic activity by metabolites is less than 1% of FLU. Consequently, clinical monitoring of plasma FLU alone may be sufficient.

show abstract

“…All tissues were homogenized in 10 ml of ice-cold physiologic saline (150 mM NaCl). Suitably diluted aliquots of these homogenates were assayed for FLU, FLU-SO, 7-OH-FLU, and FLU-NO by sensitive and specific RIAs (Aravagiri et al 1990(Aravagiri et al , 1994aMidha et al 1988;McKay et al 1990). The lower limit of determination for all RIAs was 0.1 ng of analyte/ml.…”

Section: <1mentioning

confidence: 99%

“…Individual antibody characterization and RIA procedures are detailed elsewhere (Midha et al 1988;McKay et al 1990;Aravagiri et al 1990Aravagiri et al , 1994a. Sample extracts were assayed in triplicates in subdued light.…”

Section: Extraction Of Flu and Its Metabolitesmentioning

confidence: 99%

Distribution of Fluphenazine and Its Metabolites in Brain Regions and Other Tissues of the Rat

Aravagiri

¹

,

Marder

²

,

Yuwiler

³

et al. 1995

Neuropsychopharmacology

View full text Add to dashboard Cite

Rats were given 5, 10, or 20 mg/kg oral doses of fluphenazine (FLU) dihydrochloride daily for 15 days. FLU and its sulfoxide (FL-SO), 7-hydroxy (7-OH-FLU) and N4'-oxide (FLU-NO) metabolites were assayed in plasma, liver, kidney, fat, whole brain, and brain regions by specific and sensitive radioimmunoassays (RIA). All metabolites were detected in tissues at higher levels than in plasma, and the levels increased with dose. FLU was 10- to 27-fold higher in brain regions than in plasma. Brain vs plasma levels of FLU correlated more closely than levels of its metabolites. Liver contained the highest levels of all analytes at all doses. FLU-SO was the major metabolite in brain regions (24% to 96% of FLU) and accumulated in fat 43 to 75 times more than FLU. Levels of 7-OH-FLU and FLU-NO were very low in brain (1% to 20% of FLU). FLU-SO and FLU-NO had only 1% to 3% the affinity for D1 and D2 receptors, but 7-OH-FLU had 20% the D2 and 5% the D1 affinity of FLU. The low affinity for dopamine receptors and low brain-levels of metabolites of FLU indicate that they are not likely to contribute importantly to pharmacologic responses of FLU. Also, the estimated relative "activity factor" for these compounds in the brain indicated that the contribution to neuropharmacologic activity by metabolites is less than 1% of FLU. Consequently, clinical monitoring of plasma FLU alone may be sufficient.

show abstract

Development and Application of a Radioimmunoassay for Fluphenazine Based on Monoclonal Antibodies and Its Comparison with Alternate Assay Methods

Cited by 12 publications

References 10 publications

Fluphenazine levels during maintenance treatment of recent-onset schizophrenia: relation to side effects, psychosocial function and depression

Fluphenazine levels during maintenance treatment of recent-onset schizophrenia: relation to side effects, psychosocial function and depression

Distribution of Fluphenazine and Its Metabolites in Brain Regions and Other Tissues of the Rat

Distribution of Fluphenazine and Its Metabolites in Brain Regions and Other Tissues of the Rat

Contact Info

Product

Resources

About