Document Detail

Aripiprazole in an animal model of chronic alcohol consumption and dopamine D₂ receptor occupancy in rats.
MedLine Citation:
PMID:  23421566     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Epidemiologic studies and clinical assessment of schizophrenic population have revealed a high incidence of overlap between schizophrenia and addictive disorders.
OBJECTIVE: The aim of the present investigation was to study the effect of aripiprazole in a preclinical animal model of chronic alcohol self-administration (CASA) and also to evaluate the influence of CASA on plasma pharmacokinetics and dopamine D₂ receptor (D₂R) occupancy in rats.
METHODS: The effect of oral administration of aripiprazole (1, 3, and 10 mg/kg) on 4% alcohol intake in CASA was studied for a period of 45 min after a post-dosing interval of 60 min. Brain penetration, pharmacokinetics, and D₂R occupancy of aripiprazole were evaluated in normal and CASA rats.
RESULTS: Aripiprazole reduced alcohol consumption in CASA rats by 13, 28, and 86% at 1, 3, and 10 mg/kg, respectively, and the effect reached statistical significance at 10 mg/kg (p < .01). At this behavioral effective dose, a decrease (75%) in total plasma apparent clearance and an increase in oral area under the concentration-time curve (3.98-fold) and bioavailability (3.50-fold) of aripiprazole was observed in CASA rats. Striatal D₂R occupancy and brain exposure of aripiprazole were significantly higher (∼twofold) in CASA rats when compared to normal rats (p < .01).
CONCLUSION: Chronic alcohol intake results in a significant increase in exposure of aripiprazole in plasma and brain and striatal D₂R occupancy.
SCIENTIFIC SIGNIFICANCE: Chronic alcohol intake would increase aripiprazole exposure, thus aripiprazole dose might have to be decreased (assuming this same phenomenon occurs in humans).
Ramakrishna Nirogi; Vishwottam Kandikere; Pradeep Jayarajan; Gopinadh Bhyrapuneni; Ramanatha Saralaya; Nageswararao Muddana; Renny Abraham
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The American journal of drug and alcohol abuse     Volume:  39     ISSN:  1097-9891     ISO Abbreviation:  Am J Drug Alcohol Abuse     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-20     Completed Date:  2014-01-17     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  7502510     Medline TA:  Am J Drug Alcohol Abuse     Country:  England    
Other Details:
Languages:  eng     Pagination:  72-9     Citation Subset:  IM    
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MeSH Terms
Alcohol Drinking / metabolism*
Antipsychotic Agents / administration & dosage,  pharmacokinetics*,  pharmacology*
Biological Availability
Brain / drug effects,  metabolism
Corpus Striatum / drug effects,  metabolism
Dose-Response Relationship, Drug
Models, Animal*
Piperazines / administration & dosage,  pharmacokinetics*,  pharmacology*
Quinolones / administration & dosage,  pharmacokinetics*,  pharmacology*
Receptors, Dopamine D2 / metabolism*
Self Administration
Reg. No./Substance:
0/Antipsychotic Agents; 0/Piperazines; 0/Quinolones; 0/Receptors, Dopamine D2; 82VFR53I78/aripiprazole

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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