Disease relevance of C12498

• The means (ranges) of the Css of bromperidol and reduced bromperidol corrected to the median body weight were 7.2 (1.3-17.4) and 2.2 (0.4-8.9) ng/ml, respectively [1].
• Animal toxicity (including acute- and multiple-dose toxicology and reproductive and mutagenicity studies) show that bromperidol is well tolerated [2].
• The present study thus suggests that female patients with the A1 allele show greater prolactin response to bromperidol, who may have a high risk for adverse effects associated with neuroleptic-induced hyperprolactinemia [3].

Psychiatry related information on C12498

• Interim report: high dosage bromperidol therapy of delirium tremens [4].
• Bromperidol showed a good effect on productive schizophrenic symtpoms and caused a significant reduction of accompanying depressive symptoms [5].
• According to a preliminary analysis of data, both descriptive and psychometric, bromperidol seems to be a potent antipsychotic drug without disturbing adrenolytic side-effects or sedation, with classical extrapyramidal effects of the hypertonia type [6].
• Similar numbers left the study before completion (n=20, 1 RCT, RR 0.4 CI 0.1 to 1.6) and there was no clear differences between bromperidol decanoate and placebo for a list of adverse effects (n=20, 1 RCT, RR akathisia 2.0 CI 0.21 to 18.69, RR increased weight 3.0 CI 0.14 to 65.9, RR tremor 0.33 CI 0.04 to 2.69) [7].
• No significant differences were observed for all PES items, although sulpiride was found more effective for hypochondriasis and neurotic complaint as was bromperidol for hallucination and disturbance of self-conscious [8].

High impact information on C12498

• Subjects consisted of 49 acutely exacerbated schizophrenic inpatients treated with bromperidol (30 cases, mean dose +/- SD: 11.4 +/- 4.8 mg/day) or nemonapride (19 cases, 18 mg/day) [9].
• Tissue distribution studies in the rat show a rapid and prolonged uptake into the brain, liver, and kidneys and consistently low blood concentrations that differ quantitatively from previous studies using relatively low specific activity bromperidol [10].
• This study provides in vivo evidence of involvement of CYP3A4 in the metabolism of bromperidol and reduced bromperidol [11].
• RATIONALE: A previously reported pharmacokinetic interaction between bromperidol and carbamazepine, an inducer of cytochrome P450 (CYP) 3A4, suggests possible involvement of CYP3A4 in the metabolism of bromperidol [11].
• The present study thus suggests that the polymorphic CYP2D6 is not involved in the metabolism of bromperidol and reduced bromperidol to a major extent [1].

Chemical compound and disease context of C12498

• These findings suggest that slightly higher prolactin concentration does not necessarily lead to increased risk of hyperprolactinemia during bromperidol treatment compared with haloperidol treatment [12].

Biological context of C12498

• Effects of various factors including the CYP2D6 genotype and coadministration of flunitrazepam on the steady-state plasma concentrations of bromperidol and its reduced metabolite [1].
• Biotransformation of bromperidol in rat, dog, and man [13].
• 1. The aim was to identify whether CYP3A metabolizes bromperidol (BP), an antipsychotic drug, to form 4-fluorobenzoyl-propionic acid (FBPA) in hepatic microsomes from 8-week-old male Sprague-Dawley rats and to investigate whether an inhibitor or an inducer of CYP3A affects BP pharmacokinetics in rat [14].
• Association between multidrug resistance 1 (MDR1) gene polymorphisms and therapeutic response to bromperidol in schizophrenic patients: a preliminary study [15].
• Follow-up event-related potential tests were carried out after treatment with haloperidol or bromperidol for approximately 2 months [16].

Associations of C12498 with other chemical compounds

• Establishment of new cloned enzyme donor immunoassays (CEDIA) for haloperidol and bromperidol [17].
• Double-blind study with two butyrophenone derivatives: bromperidol vs. haloperidol [18].
• Fourty-five schizophrenic inpatients were randomly assigned to bromperidol or sulpiride in an 8 week single-blind clinical trial [8].
• Within the scope of a clinical double-blind study, effects and side effects of Bromperidol and Perphenazine were compared [19].
• In in vivo and in vitro experiements the antidopaminergic action of bromperidol, evaluated by PRL release, can be considered intermediate between pimozide and haloperidol [20].

Gene context of C12498

• Involvement of CYP3A4 in the metabolism of bromperidol in vitro [21].
• Although the present study is preliminary, it is suggested that the TaqI A DRD2 polymorphism is not associated with therapeutic response to bromperidol in schizophrenic patients [22].
• Sensitive Determination of 4-(4-Bromophenyl)-4-hydroxypiperidine, a Metabolite of Bromperidol, in Rat Plasma by HPLC with Fluorescence Detection after Pre-column Derivatization Using 4-Fluoro-7-nitro-2,1,3-benzoxadiazole [23].
• These findings suggest that acute dystonia is affected by age factor, and that daily dosage or monitoring of drug concentration is unlikely to be a useful marker for the prediction of side-effects during bromperidol treatment [24].

Analytical, diagnostic and therapeutic context of C12498

• Data from additional controlled clinical trials are required to confirm the comparative antipsychotic efficacy of bromperidol and to assess whether it possesses any advantages in certain sub-types of schizophrenia [25].
• Plasma concentration of bromperidol was measured by HPLC method [3].
• A sensitive radioimmunoassay (RIA) procedure was developed to assay for bromperidol levels in human plasma after therapeutic drug administration [26].
• Determination of bromperidol in serum by automated column-switching high-performance liquid chromatography [27].
• Predose ( Cmin ) plasma levels of bromperidol in schizophrenic patients maintained on drug therapy are also reported [26].

References