Aripiprazole (air-ee-PIP-ruh-zole) (sold as Abilify) was approved by the Food and Drug Administration (FDA) on November 15, 2002 for the treatment of schizophrenia, the sixth atypical antipsychotic medication of its kind. More recently it received FDA approval for the treatment of acute manic and mixed episodes associated with bipolar disorder, and as an adjunct for the treatment of depression.^[1] Aripiprazole was developed by Otsuka in Japan; in the U.S., Otsuka America markets the drug jointly with Bristol-Myers Squibb. Annual sales approx $2.1bn.^{[citation needed]}

Pharmacology

Aripiprazole's mechanism of action is different from the other FDA-approved atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine, ziprasidone, and risperidone). Rather than antagonizing the D₂ receptor, aripiprazole appears to be a D₂ partial agonist^[2] and selective agonist.^[3] D₂ and D₃ receptor occupancy levels are high, with average levels ranging between ~71% at 2mg/day to ~96% at 40mg/day.^[4] Most atypical antypsychotics bind preferentially to extrastriatal receptors, but aripiprazole appears to be less preferential in this regard, as binding rates are high throughout the brain.^[5]

In addition to its functional selectivity at the D₂ receptor, aripiprazole is also a partial agonist at the 5-HT_1A receptor, and like the other atypical antipsychotics displays an antagonist profile at the 5-HT_2A receptor. Aripiprazole has moderate affinity for histamine and alpha-adrenergic receptors and for the serotonin transporter, and no appreciable affinity for cholinergic muscarinic receptors.^[6]

Pharmacokinetics

Aripiprazole displays linear kinetics and has an elimination half-life of approximately 75 hours. Steady-state plasma concentrations are achieved in about 14 days. Cmax (maximum plasma concentration) is achieved 3-5 hours after oral dosing. Bioavailability of the oral tablets is about 90% and the drug undergoes extensive hepatic metabolization (dehydrogenation, hydroxylation, and N-dealkylation), principally by the enzymes CYP2D6 and CYP3A4. Its only known active metabolite is dehydro-aripiprazole, which typically accumulates to approximately 40% of the aripiprazole concentration. Its elimination half-life is about 94 hours. The parenteral drug is excreted only in traces, and its metabolites, active or not, are excreted via feces and urine.^[6]

Patent status and availability

Otsuka's patent on aripiprazole expires on October 20, 2014;^[7] however, due to a pediatric extension, a generic will not become available until at least April 20, 2015.^[8] Barr Laboratories initiated a patent challenge under the Hatch-Waxman Act in March 2007.^[9] This challenge is still in court as of 11 December 2008.

Aripiprazole is available in 2mg, 5mg, 10mg, 15mg, 20mg, and 30mg tablets. Aripiprazole is also available as 10mg and 15mg orally-disintegrating tablets, 1mg/1ml solution and 7.5mg/ml intramuscular injection.

Warnings about medications with similar names

Warning flags are raised by the drug's name: the '-prazole' suffix incorrectly associates the drug with the proton pump inhibitors (such as omeprazole, pantoprazole, and lansoprazole), that are used to treat peptic ulcer disease. However, aripiprazole is in an entirely different class of drugs, and can provoke unnecessary side effects when incorrectly prescribed for peptic ulcer disease. Also, aripiprazole can be confused with "azole" antifungals, such as ketoconazole and clotrimazole.

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