Variation in the single dose pharmacokinetics of fluphenazine in psychiatric patients

Midha, K. K.; Hawes, E. M.; Hubbard, John W.; Korchinski, E. D.; McKay, G.

doi:10.1007/bf00177561

Cited by 34 publications

(3 citation statements)

References 15 publications

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“…Although there was wide inter‐subject variation in pharmacokinetic parameters, no significant difference was detected between the two groups. Similarly, no ethnic difference was observed in the pharmacokinetics of fluphenazine ( 128). Ethnic variations in response to antipsychotic drugs are summarized in Table 8.…”

Section: Ethnic Differences In the Pharmacokinetics Of Psychotropic Dmentioning

confidence: 96%

Pharmacogenetics and psychopharmacotherapy

2000

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Response to drugs can vary between individuals and between different ethnic populations. The biological (age, gender, disease and genetics), cultural and environmental factors which contribute to these variations are considered in this review. The most important aspect is the genetic variability between individuals in their ability to metabolize drugs due to expression of 'polymorphic' enzymes. Polymorphism enables division of individuals within a given population into at least two groups, poor metabolisers (PMs) and extensive metabolisers (EMs) of certain drugs. The two most extensively studied genetic polymorphisms are those involving cytochrome P450 2D6 (CYP2D6) and CYP2C19. CYP2D6 metabolizes a number of antidepressants, antipsychotics, beta-adrenoceptor blockers, and antiarrhythmic drugs. About 7% of Caucasians and 1% of Asians are PMs of CYP2D6 substrates. CYP2C19 enzyme participates in the metabolism of omeprazole, propranolol and psychotropic drugs such as hexobarbital, diazepam, citalopram, imipramine, clomipramine and amitriptyline. The incidence of PMs of CYP2C19 substrates is much higher in Asians (15-30%) than in Caucasians (3-6%). Variations in metabolism of psychotropic drugs result in variations in their pharmacokinetic parameters. This may lead to clinically significant intra- and inter-ethnic differences in pharmacological responses. Such variations are discussed in this review. Differential receptor-mediated response may play a role in ethnic differences in responses to antipsychotics and tricyclic antidepressants, but such pharmacodynamic factors remain to be systematically investigated. The results of studies of ethnic differences in response to psychopharmacotherapy appear to be discrepant, most probably due to limitations of study design, small sample size, inadequately defined study sample, and lack of control of confounding factors. The clinical value of understanding pharmacogenetics is in its use to optimize therapeutic efficacy, to prevent toxicity of those drugs whose metabolism is catalysed by polymorphic isoenzymes, and to contribute to the rational design of new drugs. Finally, applications and impact of pharmacogenetics in the field of psychopharmacotherapy are discussed.

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Section: Ethnic Differences In the Pharmacokinetics Of Psychotropic Dmentioning

confidence: 96%

Pharmacogenetics and psychopharmacotherapy

2000

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“…The results of a recent study comparing response to antipsychotic medications among three ethnic groups (black, mixed descent, white) showed significant differences among the groups in reductions in psychotic symptoms (Emsley et al 2002), but these findings are not supported by earlier reports (Strickland et al 1991; Lin and Poland 1995; Lin et al 1995; Frackiewicz et al 1997). Furthermore, the few studies (Midha et al 1988 a , 1988 b ) that have compared African-American and Caucasian patients with respect to pharmacokinetic properties of antipsychotic medications have found no differences between the groups. Some evidence does suggest that up to one-third of African-Americans possess genetic polymorphisms of the enzymes that metabolize most psychopharmacologic agents, resulting in slowed metabolism and the likelihood of enhanced adverse drug effects (Lin and Poland 1995; Lin et al 1995; Frackiewicz et al 1997), but the clinical significance of these metabolic differences has not been tested empirically.…”

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confidence: 99%

Racial Disparity in the Pharmacological Management of Schizophrenia

Kreyenbuhl

Zito

Boyer

et al. 2003

Schizophrenia Bulletin

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This study investigated racial differences in the prescription of psychopharmacologic treatments to individuals with schizophrenia. Data were derived from a patient survey and medical record review for 344 persons with schizophrenia recruited from outpatient psychiatric facilities in two States in the Schizophrenia Patient Outcomes Research Team study. African-Americans were three times more likely to receive depot antipsychotic medications (odds ratio [OR]: 2.91; 95% confidence interval [CI]: 1.68-5.01) and 76 percent less likely to receive new-generation antipsychotic medications (OR: 0.24; 95% CI: 0.12-0.46), compared to their Caucasian counterparts. Chlorpromazine-equivalent antipsychotic dosages did not differ significantly between African-American and Caucasian patients. Compared to Caucasians, a larger proportion of African-Americans received antiparkinsonian medications (63% vs. 48%, chi2 = 7.01; df = 1; p = 0.008), but African-Americans were less than half as likely to receive adjunctive psychopharmacologic treatments (OR: 0.43; 95% CI: 0.27-0.71). Pronounced racial variations in the psychopharmacologic management of schizophrenia in typical clinical practice settings were observed and persisted when analyses were adjusted for selected patient demographic and clinical characteristics. A prospective, longitudinal evaluation is warranted to determine whether the observed patterns of prescribing are associated with poorer therapeutic outcomes in minority patients.

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“…Plasma concentrations then rapidly decline and a slow ~ elimination phase follows. [43] Patients treated with fluphenazine 5 to 20 mg/day show optimal clinical response within 2 weeks of initiating treatment. [42] The t!l2~ of fluphenazine varies from 5 to 27 hours.l 43 ] There is also a 5-to II-fold individual variation in Cmax and AVC.…”

Section: Fluphenazinementioning

confidence: 99%

Emergency Treatment of Psychotic Symptoms

Milton

Jann

1995

Clinical Pharmacokinetics

181

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Psychotic symptoms related to mental and medical disorders can pose a medical emergency. Selecting an appropriate antipsychotic medication to treat this emergency is based on the clinical situation, preferred route of administration, pharmacokinetic profile of the antipsychotic and the medications currently being taken by the patient. Intramuscular preparations are usually preferred over oral medication when the patients are not co-operative and require drugs with a faster onset of action and good bioavailability. High potency antipsychotics such as haloperidol and fluphenazine are effective in stabilising patients with psychotic symptoms quickly. Loxapine is an alternative when sedation is necessary and molindone is useful if a short-acting antipsychotic is required. Rapid neuroleptisation with intramuscular preparations of antipsychotic achieves therapeutic drug concentrations more rapidly, and also provides optimal control of psychotic symptoms. If the patient is cooperative, liquid oral preparations can be used; they are as effective as intramuscular formulations. If long term treatment with an antipsychotic in necessary and patients are stabilised, they can be switched from intramuscular to oral preparations. The oral dose is usually 1.5 to 5 times the total intramuscular dose per day, based on the bioavailability of the antipsychotic medication. If the patient is currently taking antipsychotic medication when the emergency situation occurs, it is usually adequate to increase the dose of antipsychotic drug. Appropriate dose adjustment or antipsychotic selection is necessary when drug interactions are expected. An in-depth knowledge of the pharmacokinetic profile and drug interaction profile of antipsychotic in necessary for the selection of the appropriate antipsychotic for any given emergency situation.

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Variation in the single dose pharmacokinetics of fluphenazine in psychiatric patients

Cited by 34 publications

References 15 publications

Pharmacogenetics and psychopharmacotherapy

Pharmacogenetics and psychopharmacotherapy

Racial Disparity in the Pharmacological Management of Schizophrenia

Emergency Treatment of Psychotic Symptoms

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