title: Effect of combination of aripiprazole with carbamazepine and fluvoxamine on liver functions in experimental animals.
abstract: OBJECTIVE
  Aripiprazole, a new atypical antipsychotic drug extensively metabolized by enzyme CYP3A4, is found to produce asymptomatic elevation of serum transaminase levels on long-term treatment. The present study aims to evaluate the hepatotoxic effect of aripiprazole when coprescribed with carbamazepine and fluvoxamine.
  
  
  METHODS
  The rats were subjected to chronic treatment with two different doses, therapeutic dose (TD) and maximum therapeutic dose (MTD), of aripiprazole in combination with carbamazepine and fluvoxamine. The changes in hepatic function was assessed by various biochemical liver enzyme markers like serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total bilirubin, histological studies, and physical parameters (liver weight, liver volume, and body weight).
  
  
  RESULTS
  The combination of aripiprazole with fluvoxamine at both TD and MTD showed the hepatic damage and significant elevation in serum transaminase level which is supported by histological reports. The coadministration of aripiprazole with carbamazepine leads to significant decrease in blood concentration of aripiprazole possibly due to induction of enzyme CYP3A4 resulting in loss or reduction of clinical efficacy.
  
  
  CONCLUSIONS
  There would be an accumulation of aripiprazole when coadministered with fluvoxamine, a known inhibitor of CYP3A4, leading to hepatic damage and reduction in aripiprazole when administered along with carbamazepine. Therefore, aripiprazole with fluvoxamine and carbamazepine should be coprescribed with caution. The patients should be monitored for signs of adverse effects like hepatic damage or decreased efficacy of these drugs.
authors.affiliation: Department of Pharmacology, NGSM Institute of Pharmaceutical Sciences, Deralakatte, Mangalore, Karnataka, India.
authors.forename: Chakrakodi S
authors.initials: CS
authors.lastname: Shastry
authors.forename: Aboobakar A
authors.initials: AA
authors.lastname: Shafeeque
authors.forename: Badavanahalli J
authors.initials: BJ
authors.lastname: Ashwathnarayana
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000633:toxicity*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000633:toxicity*; D000068180:Aripiprazole; D024443:Aspartate Aminotransferase, Cytoplasmic / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001835:Body Weight; D002220:Carbamazepine / Q000009:adverse effects / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D016666:Fluvoxamine / Q000009:adverse effects / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D009929:Organ Size; D010879:Piperazines / Q000009:adverse effects / Q000633:toxicity*; D015363:Quinolones / Q000009:adverse effects / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000637:Transaminases / Q000097:blood
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D015415:Biomarkers; D010879:Piperazines; D015363:Quinolones; D002220:Carbamazepine; D000068180:Aripiprazole; D024443:Aspartate Aminotransferase, Cytoplasmic; D000637:Transaminases; C022393:phosphoserine aminotransferase; D000469:Alkaline Phosphatase; D016666:Fluvoxamine; D001663:Bilirubin
keywords: Aripiprazole; antipsychotic drug; carbamazepine; drug-drug interaction; fluvoxamine; hepatotoxicity