Radioimmunoassay for the Sulfoxide Metabolite of Trifluoperazine and its Application to a Kinetic Study in Humans

Aravagiri, Manickam; Hawes, E. M.; Midhax, K.K.

doi:10.1002/jps.2600731015

Cited by 14 publications

(8 citation statements)

References 15 publications

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“…1), haloperidol (Balant-Gorgia et al 1984), levomepromazine (Dahl 1976) and perphenazine (Larsson et al 1984). The results of these studies together with other data on metabolite-toparent-drug plasma concentration ratios suggest that there are large interindividual variations in the extent of presystemic metabolism of phenothiazine drugs (Aravagiri et al 1984;Dahl 1976;. Indeed, this may be a major reason for the large interindividual variations in plasma levels of phenothiazine drugs.…”

Section: Interindividual Variations In Presystemic Metabolismmentioning

confidence: 84%

“…This has 40 been demonstrated for chlorpromazine (Curry 1981), levomepromazine (Dahl et al 1982a), loxapine (Cooper & Kelly 1979), thioridazine (Axelsson & Martensson 1977), haloperidol Korpi et al 1983b) and trifluoperazine (Aravagiri et al 1984).…”

Section: Interpatient Variation In Plasma Levelsmentioning

confidence: 86%

“…Plasma concentrations of drug metabolites as high as or higher than that of the parent compound have been observed after oral doses of levomepromazine (Dahl et al 1982a), loxapine (Cooper & Kelly 1979 1977), and trifluoperazine (Aravagiri et al 1984). …”

Section: Active Metabolites 0/ Antipsychotic Drugsmentioning

confidence: 96%

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Plasma Level Monitoring of Antipsychotic Drugs Clinical Utility

Dahl

1986

Clinical Pharmacokinetics

145

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The steady-state plasma concentrations of antipsychotic drugs show large interpatient variations but remain relatively stable from day to day in each individual patient. Monitoring of antipsychotic drug concentrations in plasma might be of value provided the patients are treated with only 1 antipsychotic drug. Some studies have reported a relationship between therapeutic response and serum antipsychotic drug 'concentrations' as measured using the radioreceptor assay (RRA) method, which measures dopamine receptor-blocking activity in plasma. Most studies, however, have failed to demonstrate such a relationship, and the RRA does not seem to provide the generally useful tool for plasma concentration monitoring of antipsychotic drugs that was hoped for initially. A lack of correlation between dopamine receptor-blocking activity in plasma and therapeutic response may be due to differences in the blood-brain distribution of both antipsychotic drugs and their active metabolites. Chemical assay methods (e.g. GLC and HPLC) have been used in studies which examined the relationships between therapeutic response and antipsychotic drug concentrations in red blood cells and in plasma. It seems that for these drugs, measuring red blood cell concentrations does not offer any significant advantage over measuring plasma concentrations. Reasonably controlled studies of plasma concentration-response relationships using randomly allocated, fixed dosages of chlorpromazine, fluphenazine, haloperidol, perphenazine, sulpiride, thioridazine and thiothixene have been published but often involve relatively few patients. A correlation between therapeutic response and plasma concentrations of thioridazine and its metabolites has not been demonstrated, and plasma level monitoring of thioridazine and its metabolites therefore appears to have no clinical value. Clinical behavioural deterioration concomitant with high plasma concentrations of chlorpromazine and haloperidol have been reported. A dosage reduction might be considered after 2 to 4 weeks' treatment in non-responders who have plasma chlorpromazine concentrations above 100 to 150 micrograms/L or plasma haloperidol concentrations above 20 to 30 micrograms/L. Non-responders and good responders to chlorpromazine treatment, however, have plasma drug concentrations in the same range, and a therapeutic range of plasma chlorpromazine levels has not been defined. Therapeutic plasma haloperidol concentrations (i.e. 'window') in the range of 5 to 20 micrograms/L have been reported by some investigators, but others have found no such relationship.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Interindividual Variations In Presystemic Metabolismmentioning

confidence: 84%

Section: Interpatient Variation In Plasma Levelsmentioning

confidence: 86%

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Plasma Level Monitoring of Antipsychotic Drugs Clinical Utility

Dahl

1986

Clinical Pharmacokinetics

145

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“…Recently, radioimmunoassays have been described for the measurement of the sulfoxide (Aravagiri et al 1984), N4-oxide (Aravagiri et al 1986), and 7-hydroxy (Aravagiri et al 1985) metabolites of trifluoperazine in plasma. Preliminary studies suggest that one of the causes of intersubject variation may relate to differences between individuals in Offprint requests to: K.K.…”

mentioning

confidence: 99%

“…Preliminary studies suggest that one of the causes of intersubject variation may relate to differences between individuals in Offprint requests to: K.K. Midha the extent of conversion of the parent drug into its sulfoxide (Aravagiri et al 1984) and N4-oxide (Aravagiri et al 1986) metabolites during the first passage through the gut wall, liver, and lung before entering the systemic circulation (presystemic absorption). The unconjugated 7-hydroxy metabolite appeared to be formed less extensively during presystemic absorption (Aravagiri et al 1985), but there was wide variation in the apparent elimination half-life and in the ratio of the area under the plasma concentration versus time curve (AUC) of the metabolite to that of the parent drug.…”

mentioning

confidence: 99%

A pharmacokinetic study of trifluoperazine in two ethnic populations

et al. 1988

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The single dose pharmacokinetics of trifluoperazine (5 mg, Stelazine) were investigated in black (n = 25) and white (n = 32) healthy male subjects. Plasma samples were harvested over 24 h and analysed by a GLC-MS method. There were wide intersubject variations in all pharmacokinetic parameters examined, including Cmax, AUC, apparent oral volume of distribution at steady state, and elimination half-life. For each of these parameters the distribution was positively skewed in both blacks and whites and the geometric mean gave a better estimate of central tendency than the corresponding arithmetic mean. In all pharmacokinetic parameters examined there was no significant difference detected between black and white subjects or between smokers and non-smokers.

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