Fluphenazine pharmacokinetics and therapeutic response

Dysken, Maurice W.; Javaid, Javaid I.; Chang, Sun‐Yran; Schaffer, Charles B.; Shahid, Agha; Davis, John M.

doi:10.1007/bf00422403

Cited by 82 publications

(37 citation statements)

References 32 publications

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“…Mavroidis et al (1984) found a curvilinear relationship between clinical response and plasma levels, with levels above 0.7 ng/ml being associated with a less favorable outcome when compared with lower levels. Dysken et al (1981) found that three patients who had fluphenazine levels greater than 2.8 ng/ml did poorly, which also suggested a curvili near relationship. The one patient in our study with a level of more than 2.8 (acutally 3.5 ng/ml) remained unrelapsed.…”

Section: Discussionmentioning

confidence: 94%

“…In a study of (oral) fluphenazine hydrochloride, Mavroidis and his coworkers (1984) found that the lowest level of fluphenazine detectable with their assay, 0.13 ng/ml, was within the therapeutic range. Dysken et al (1981) found that levels of fluphenazine above 0.2 ng/ml were effective. Since the level of sensitivity of our assay was 0.15 ng/ml, it is possible that we did not find a threshold because the lowest amount of fluphenazine detectable was within the therapeutic range.…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies indicate that patients treated in this manner commonly have a clinical response with plasma levels in the subnanogram range (Dysken et al 1981 ;Mavroidis et al 1984;Tune et al 1980;Dudley et al 1983).…”

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confidence: 99%

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Fluphenazine plasma levels in patients receiving low and conventional doses of fluphenazine decanoate

et al. 1986

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Plasma fluphenazine concentrations (FLU) were measured in 45 patients with schizophrenic disorders who participated in a double-blind comparison of 5 and 25 mg fluphenazine decanoate (FD). The rise in plasma level of FLU 24 h after a "test dose" was significantly correlated with steady state FLU concentration at 12 weeks (for 5 mg patients, r = 0.45, P = 0.04; for 25 mg, r = 0.78, P = 0.005). Patients who had low FLU at baseline required nearly 6 months to reach a steady state when they received 25 mg. Patients who received 5 mg and had low FLU at baseline continued to demonstrate relatively low plasma levels for the entire 1st year. Although the mean FLU at 6 months was lower for patients who relapsed during the subsequent 18 months (0.57 ng/ml for relapsers vs 1.01 ng/ml for nonrelapsers), this difference was not statistically significant. When plasma levels from both dosage groups were combined, FLU at 12 weeks correlated significantly with factor scores for akinesia (r = 0.52, P = 0.002) and BPRS cluster scores for retardation (r = 0.52, P = 0.002). These results indicate that the measurement of fluphenazine plasma levels may be useful in determining when patients treated with FD are receiving drug doses which are likely to cause discomforting side effects.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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Fluphenazine plasma levels in patients receiving low and conventional doses of fluphenazine decanoate

et al. 1986

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“…chotic drugs and clinical response (Dysken et al, 1981;Bolvig Hansen and Larsen, 1985;Van Putten er al., 1992) while no definite relationship could be found in other studies (Van Putten et al, 1981;Volavoka et al, 1992). Previously, we studied the steady-state serum kinetics of zotepine.…”

Section: Introductionmentioning

confidence: 98%

A study of the therapeutic spectrum of a fixed‐dose of zotepine and its relationship with serum concentrations of the drug

Kondo

Otani

Ishida

et al. 1993

Human Psychopharmacology

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The therapeutic spectrum of zotepine, an antipsychotic drug, and its relationship with serum concentrations of the drug were investigated by a fixed-dose study (100mg/day in the first week, and 200mg/day for the next 3 weeks) in 20 schizophrenic in-patients. The mean percentages of symptom reduction in total Brief Psychiatric Rating Scale (BPRS) and three subgroups were 63.4 per cent for total, 64-4 per cent for positive symptoms, 41.8 per cent for negative symptoms and 74.2 per cent for anxiety-depression respectively. Total, positive and negative symptoms were significantly reduced after 2 weeks (p < 0-OI), while a significant reduction in anxiety-depression symptoms was already found after 1 week (p < 0.01). There were significant differences in the values of percentage improvement in total and positive symptoms after 2 weeks (p < 0.05) and negative symptoms after 1 week (p < 0-05) between responders (more than 50 per cent reduction in total BPRS scores at the end of the study) and nonresponders.In 18 patients (90 per cent), the clinical response at 2 weeks corresponded well to the final outcome. No definite relationship was found between serum zotepine concentrations and the clinical efficacy.

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“…Steady state plasma levels of fluphenazine in patients are in the low ng/ml range whether the drug is administered orally (Dysken et al 1981 ;Harris et al 1982;Mavroidis et al 1984a, b: Hitzemann et al 1985 or by intramuscular injection (Curry et al 1979;Wiles and Gelder 1979;Harris et al 1982;Altamura et al 1985;Brown and Silva 1985;Chang et al 1985;Marder et al 1986a, b). Consequently, plasma levels of fluphenazine are even harder to measure than those of other phenothiazines and there are relatively few plasma level studies on this piperazine type phenothiazine antipsychotic agent.…”

mentioning

confidence: 99%

Variation in the single dose pharmacokinetics of fluphenazine in psychiatric patients

et al. 1988

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The single dose pharmacokinetics of fluphenazine (2 x 5 mg tablets, Prolixin) were studied in 21 drug free male psychiatric patients (12 black, 9 white). Plasma samples were harvested over a period of 48 h while the patients were on a strictly controlled diet. The results showed wide interpatient variations in all pharmacokinetic parameters including Cmax, AUC, apparent oral clearance, and elimination half-life. It was determined for each of these parameters that the geometric mean gave a better estimate of central tendency than the corresponding arithmetic mean and the distribution was skewed and leptokurtotic. There was no significant difference between blacks and whites in any pharmacokinetic parameter examined. Considerable variations and marked undulations in the elimination portion of the plasma concentration versus time profiles were evident, possibly indicating biliary recycling of the drug. These undulations made it difficult to determine elimination rate constants for several of the patients. Hydrolysis or plasma samples from one patient demonstrated that the conjugate(s) of fluphenazine was present in three to four times the concentration of the unchanged drug.

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Fluphenazine pharmacokinetics and therapeutic response

Cited by 82 publications

References 32 publications

Fluphenazine plasma levels in patients receiving low and conventional doses of fluphenazine decanoate

Fluphenazine plasma levels in patients receiving low and conventional doses of fluphenazine decanoate

A study of the therapeutic spectrum of a fixed‐dose of zotepine and its relationship with serum concentrations of the drug

Variation in the single dose pharmacokinetics of fluphenazine in psychiatric patients

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