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Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals

Pharmaceuticals -> Antipsychotics

0.00001%

<0.3 [ug/mL] (The mean of the results at pH 7.4)

Breast Feeding; Lactation; Milk, Human; Antipsychotic Agents

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

Positive

4.39206747

2.7

Thermo LTQ

Electrospray ionization

formic acid (5.3nM)

205.8 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

203.5 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

202.75 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Danger

H301 (62.7%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P264, P270, P273, P280, P301+P316, P301+P317, P318, P321, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 51 reports by companies from 20 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H226: Flammable liquid and vapor [Warning Flammable liquids]

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including aripiprazole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary. Use water spray to cool unopened containers.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Storage class (TRGS 510): Flammable liquids

ACCIDENTAL RELEASE MEASURES. Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapours accumulating to form explosive concentrations. Vapours can accumulate in low areas.; Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.; Methods and materials for containment and cleaning up: Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations.

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid inhalation of vapour or mist. Keep away from sources of ignition - No smoking.Take measures to prevent the build up of electrostatic charge.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Body Protection: Complete suit protecting against chemicals, Flame retardant antistatic protective clothing., The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Skin protection: Handle with gloves.

Eye/face protection: Face shield and safety glasses Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

No specific information is available on the treatment of overdose with aripiprazole. An electrocardiogram should be obtained in case of overdosage and if QT interval prolongation is present, cardiac monitoring should be instituted. Otherwise, management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Close medical supervision and monitoring should continue until the patient recovers. Consider charcoal and hemodialysis. (A308)

Substrates of Hepatic Microsomal Enzymes: Substrates of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4; pharmacokinetic interaction unlikely.

Hypotensive Agents: Potential pharmacologic interaction (additive hypotensive effects)

Famotidine: Coadministration of aripiprazole (given in a single dose of 15 mg) with a 40-mg single dose of the H2 antagonist famotidine, a potent gastric acid blocker, decreased the solubility of aripiprazole and, hence, its rate of absorption, reducing by 37% and 21% the Cmax of aripiprazole and dehydro-aripiprazole, respectively, and by 13% and 15%, respectively, the extent of absorption (AUC). No dosage adjustment of aripiprazole is required when administered concomitantly with famotidine.

Valproate: When valproate (500-1500 mg/day) and aripiprazole (30 mg/day) were coadministered at steady state, the C max and AUC of aripiprazole were decreased by 25%. No dosage adjustment of aripiprazole is required when administered concomitantly with valproate.

For more Interactions (Complete) data for ARIPIPRAZOLE (12 total), please visit the HSDB record page.

Health effetcs include hyperpyrexia,muscle rigidity,altered mental status,and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Other effects may include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology (RxList, A308).

Liver test abnormalities have not been reported to occur in patients on long term therapy with aripiprazole, but most studies have not provided information on serum enzyme results. Despite its widescale use, aripiprazole has been implicated in only rare and isolated cases of clinically apparent liver injury in the literature. All reported cases have been hepatocellular arising after 1 to 3 months of therapy and with accelerated onset in one instance upon re-exposure. Immunoallergic and autoimmune features were not present. Most cases have been anicteric, and none were fatal or resulted in chronic injury. Aripiprazole has not been reported among agents implicated in large case series of drug induced liver injury. The product label for aripiprazole mentions that hepatitis and jaundice have been reported, but no specific details were provided. Thus, clinically apparent liver injury from aripiprazole must be very rare.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2.5X10+4(SRC), determined from a structure estimation method(2), indicates that aripiprazole is expected to be immobilein soil(SRC). The estimated pKa1 of aripiprazole is 7.46(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of the neutral species of aripiprazole from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.7X10-17 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Aripiprazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.2X10-13 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2015).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2.5X10+4(SRC), determined from a structure estimation method(2), indicates that aripiprazole is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 7.7X10-17 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 1500(SRC), from an estimated log Kow of 5.30(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is very high(SRC). Biodegradation data in water were not available(SRC, 2015).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), aripiprazole, which has an estimated vapor pressure of 3.2X10-13 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase. Particulate-phase aripiprazole may be removed from the air by wet and dry deposition(SRC). Aripiprazole contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Although the side effects of aripiprazole are similar to those found in typical and atypical antipsychotics, the degree of extrapyramidal symptoms (EPS) and metabolic syndromes is less due to receptor specificity. EPS, such as akathisia, Parkinsonian features such as resting tremor and shuffling gait, acute dystonic reactions, oculogyric crises, opisthotonos, and tardive dyskinesia, are manageable with benztropine or sodium benzoate. Aripiprazole is associated with lower incidences of weight gain, hypercholesterolemia, glucose dysregulation, cardiovascular abnormalities, and hyperprolactinemia. Hyperprolactinemia may manifest as galactorrhea, gynecomastia in men, sexual dysfunction, amenorrhea, or off-cycle bleeding. Other possible side effects of aripiprazole include somnolence, nausea, vomiting, akathisia, and lightheadedness. Antipsychotics agent use requires caution in older adults because it can cause or exacerbate the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; thus, it is crucial to monitor sodium during initiation and dosage adjustment. Children and adolescents are more susceptible than older patients to experience EPS, weight gain, and other metabolic side effects. The FDA also recently identified an association between aripiprazole use and compulsive or uncontrollable urges to engage in sex, gamble, binge eat, and shop.

IDENTIFICATION AND USE: Aripiprazole is used IM for the acute management of agitation associated with schizophrenia or bipolar disorder, mixed or manic, in adults for whom treatment with aripiprazole is appropriate and who require an IM antipsychotic agent for rapid control of behaviors that interfere with diagnosis and care (e.g., threatening behaviors, escalating or urgently distressing behavior, self-exhausting behavior). Aripiprazole is used orally for the acute treatment of irritability associated with autistic disorder. Aripiprazole is used orally as an adjunct to antidepressants for the acute treatment of major depressive disorder in adults. Aripiprazole is used orally as monotherapy or as an adjunct to either lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults and pediatric patients 10-17 years of age. The drug also is used orally as monotherapy or as adjunctive therapy with lithium or valproate for the maintenance treatment of bipolar I disorder in adults and pediatric patients 10-17 years of age. Aripiprazole is used orally for the acute and maintenance treatment of schizophrenia in adults and adolescents 13-17 years of age. HUMAN EXPOSURE AND TOXICITY: A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including aripiprazole. Two possible cases of NMS occurred during aripiprazole treatment in the premarketing worldwide clinical database. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. ANIMAL STUDIES: In female mice, the incidences of pituitary gland adenomas and mammary gland adenocarcinomas and adenoacanthomas were increased at dietary dose of 3 to 30 mg/kg/day. Female rats were treated with oral doses of 2, 6, and 20 mg/kg/day of aripiprazole from 2 weeks prior to mating through day 7 of gestation. Estrus cycle irregularities and increased corpora lutea were seen at all doses, but no impairment of fertility was seen. Increased pre-implantation loss was seen at 6 and 20 mg/kg, and decreased fetal weight was seen at 20 mg/kg. Pregnant rabbits were treated with oral doses of 10, 30, and 100 mg/kg/day of aripiprazole during the period of organogenesis. Decreased maternal food consumption and increased abortions were seen at 100 mg/kg. Treatment caused increased fetal mortality (100 mg/kg), decreased fetal weight (30 and 100 mg/kg), increased incidence of a skeletal abnormality (fused sternebrae at 30 and 100 mg/kg) and minor skeletal variations (100 mg/kg). Aripiprazole and a metabolite (2,3-DCPP) were clastogenic in the in vitro chromosomal aberration assay in CHL cells with and without metabolic activation. The metabolite, 2,3-DCPP, produced increase in numerical aberrations in the in vitro assay in CHL cells in the absence of metabolic activation. A positive response was obtained in the in vivo micronucleus assay in mice, however,the response was shown to be due to a mechanism not considered relevant to humans.

According to FDA reports, there have been 76 cases of aripiprazole overdose. These include instances of both deliberate and accidental overdose in combination with other substances. There is currently no known antidote for aripiprazole overdose. However, early charcoal administration partially prevents the absorption of the drug if it is ingested orally, e.g., a tablet. Management of aripiprazole overdose should focus on supportive therapy. The clinician should obtain an EKG to identify any cardiac arrhythmias, such as QTc prolongation.

Aripiprazole's antipsychotic activity is likely due to a combination of antagonism at D2 receptors in the mesolimbic pathway and 5HT2A receptors in the frontal cortex. Antagonism at D2 receptors relieves positive symptoms while antagonism at 5HT2A receptors relieves negative symptoms of schizophrenia. Aripiprazole exhibits high affinity for dopamine D2 and D3, serotonin 5-HT1A and 5- HT2A receptors, moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, alpha1-adrenergic and histamine H1 receptors and moderate affinity for the serotonin reuptake pump. Aripiprazole has no appreciable affinity for cholinergic muscarinic receptors. Aripiprazole functions as a partial agonist at the dopamine D2 and the serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A receptor.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of aripiprazole can be estimated to be 2.5X10+4(SRC). According to a classification scheme(2), this estimated Koc value suggests that aripiprazole is expected to be immobile in soil. The estimated pKa of aripiprazole is 7.46(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

/SIGNS AND SYMPTOMS/ A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including aripiprazole. Two possible cases of NMS occurred during aripiprazole treatment in the premarketing worldwide clinical database. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.

/SIGNS AND SYMPTOMS/ Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment, has been reported in patients receiving antipsychotic agents, including rare cases associated with aripiprazole therapy.

/SIGNS AND SYMPTOMS/ A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) may occur with administration of antipsychotic drugs, including aripiprazole. Rare cases of NMS occurred during aripiprazole treatment in the worldwide clinical database. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to exclude cases where the clinical presentation includes both serious medical illness (eg, pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology.

/SIGNS AND SYMPTOMS/ A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown. The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.

For more Human Toxicity Excerpts (Complete) data for ARIPIPRAZOLE (7 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including aripiprazole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

N05AX12

N - Nervous system

QN - Nervous system

Aripiprazole exhibits high affinity for dopamine D₂ and D₃, serotonin 5-HT_1a and 5-HT_2a receptors (Ki values of 0.34 nM, 0.8 nM, 1.7 nM, and 3.4 nM, respectively), moderate affinity for dopamine D₄, serotonin 5-HT_2c and 5-HT₇, alpha₁-adrenergic and histamine H₁ receptors (Ki values of 44 nM, 15 nM, 39 nM, 57 nM, and 61 nM, respectively), and moderate affinity for the serotonin reuptake site (Ki=98 nM). Aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC₅₀>1000 nM).

The antipsychotic action of aripiprazole is likely due to its partial agonist activity on D2 and 5-HT_1A receptors as well as its antagonist activity at 5-HT_2A receptors; however, the exact mechanism has not been fully elucidated. One of the mechanisms that have been proposed is that aripiprazole both stimulates and inhibits dopamine as it engages the D2 receptor. It lowers dopamine neuronal firing at high dopamine concentrations and increases dopamine firing at low concentrations. Its partial agonist activity gives aripiprazole an intermediate level of dopaminergic neuronal tone between full agonist and antagonist of the D2 receptor. In addition, some adverse effects may be due to action on other receptors. For example, orthostatic hypotension may be explained by antagonism of the adrenergic alpha-1 receptors.

The exact mechanism of antipsychotic action of aripiprazole has not been fully elucidated but, like that of other atypical antipsychotic agents (e.g.,olanzipine, risperidone, ziprasidon), may involve the drug's activity at dopamine D2 and serotonin type (5-HT1A) and type 2 (5-HT2A) receptors. However, aripiprazole appears to differ from other atypical antipsychotic agents because the drug demonstrates partial agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptors. Antagonism at other receptors (e.g., alpha1-adrenergic receptors, histamine H1 receptors) may contribute to other therapeutic and adverse effects (e.g., orthostatic hypotension, somnolence) observed with aripiprazole.

...Aripiprazole exhibits typical antagonism at dopamine (D2) receptors in the mesolimbic pathway, as well as having unique partial agonist activity at D2 receptors in the mesocortical pathway. As exemplified by other atypical antipsychotics, it displays strong 5-HT(2a) receptor antagonism and is similar to ziprasidone in also having agonistic activity at the 5-HT(1a) receptor. Among the atypical antipsychotics, aripiprazole displays the lowest affinity for alpha(1)adrenergic (alpha(1)), histamine (H1) and muscarinic (M1) receptors. This combination of effects may be responsible for its efficacy in positive and negative symptoms of schizophrenia and in bipolar disorder. ...Other early data suggest that aripiprazole may induce reductions in plasma prolactin, as well as in plasma glucose and lipid profiles ...

The mean elimination half-lives are about 75 hours and 94 hours for aripiprazole and dehydro-aripiprazole, respectively. For populations that are poor CYP2D6 metabolizers, the half-life of aripiprazole is 146 hours and these patients should be treated with half the normal dose. Other studies have reported a half-life of 61.03±19.59 hours for aripiprazole and 279±299 hours for the active metabolite.

The mean elimination half-lives are about 75 hours and 94 hours for aripiprazole and dehydro-aripiprazole, respectively.

Aripiprazole is metabolized primarily by three biotransformation pathways: dehydrogenation, hydroxylation, and N-dealkylation. Based on in vitro studies, CYP3A4 and CYP2D6 enzymes are responsible for the dehydrogenation and hydroxylation of aripiprazole, and N-dealkylation is catalyzed by CYP3A4. Aripiprazole is the predominant drug moiety in systemic circulation. At steady-state, dehydro-aripiprazole, the active metabolite, represents about 40% of aripiprazole AUC in plasma.

Aripiprazole is extensively metabolized in the liver principally via dehydrogenation, hydroxylations, and N-dealkylation by the cytochrome P-450 (CYP) 2D6 and 3A4 isoenzymes. The major active metabolite of aripiprazole, dehydro-aripiprazole, exhibits affinity for D2 receptors similar to that of the parent compound and represents approximately 40% of the aripiprazole area under the concentration-time curve (AUC) in plasma. Steady-state plasma concentrations of both aripiprazole and dehydro-aripiprazole are achieved within 14 days.

ABILIFY activity is presumably primarily due to the parent drug, aripiprazole, and to a lesser extent, to its major metabolite, dehydro-aripiprazole, which has been shown to have affinities for D2 receptors similar to the parent drug and represents 40% of the parent drug exposure in plasma.

Aripiprazole has known human metabolites that include 2,3-dichlorophenylpiperazine, dehydro-aripiprazole, 4-Hydroxyaripiprazole, and 4-[(2-oxo-3,4-dihydro-1H-quinolin-7-yl)oxy]butanal.

Aripiprazole is metabolized primarily by three biotransformation pathways: dehydrogenation, hydroxylation,and N-dealkylation.Based on in vitro studies,CYP3A4 and CYP2D6 enzymes are responsible for dehydrogenation and hydroxylation of aripiprazole, and N-dealkylation is catalyzed by CYP3A4.Aripiprazole is the predominant drug moiety in the systemic circulation. At steady-state, dehydro-aripiprazole, the active metabolite, represents about 40% of aripiprazole AUC in plasma (RxList, A308). Route of Elimination: Less than 1% of unchanged aripiprazole was excreted in the urine and approximately 18% of the oral dose was recovered unchanged in the feces. Half Life: 75-146 hours

82VFR53I78

ARIPIPRAZOLE

Established Pharmacologic Class [EPC] - Atypical Antipsychotic

Aripiprazole is an Atypical Antipsychotic.

ARIPIPRAZOLE

Atypical Antipsychotic [EPC]

Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.

Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.

Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT1 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT1 receptor subtypes.

Drugs that bind to and activate dopamine receptors.

Drugs that bind to but do not activate SEROTONIN 5-HT2 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT2 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more specific 5-HT2 receptor subtypes.

Compounds and drugs that bind to and inhibit or block the activation of DOPAMINE D2 RECEPTORS.

Tablet: Aripiprazole is well absorbed after administration of the tablet, with peak plasma concentrations occurring within 3 hours to 5 hours; the absolute oral bioavailability of the tablet formulation is 87%. ABILIFY can be administered with or without food. Administration of a 15 mg ABILIFY tablet with a standard high-fat meal did not significantly affect the Cmax or AUC of aripiprazole or its active metabolite, dehydro-aripiprazole, but delayed Tmax by 3 hours for aripiprazole and 12 hours for dehydro-aripiprazole. Oral Solution: Aripiprazole is well absorbed when administered orally as the solution. At equivalent doses, the plasma concentrations of aripiprazole from the solution were higher than that from the tablet formulation. In a relative bioavailability study comparing the pharmacokinetics of 30 mg aripiprazole as the oral solution to 30 mg aripiprazole tablets in healthy subjects, the solution-to-tablet ratios of geometric mean Cmax and AUC values were 122% and 114%, respectively. The single-dose pharmacokinetics of aripiprazole were linear and dose-proportional between the doses of 5 mg to 30 mg. Extended-release injectable suspension, bimonthly injection: Aripiprazole absorption into the systemic circulation is prolonged following gluteal intramuscular injection due to the low solubility of aripiprazole particles. The release profile of aripiprazole from ABILIFY ASIMTUFII results in sustained plasma concentrations over 2 months following gluteal injection(s). Following multiple doses, the median peak:trough ratio for aripiprazole following an ABILIFY ASIMTUFII dose is 1.3, resulting in a flat plasma concentration profile with Tmax ranging between 1 to 49 days following multiple gluteal administrations of 960 mg.

Following a single oral dose of [14C]-labeled aripiprazole, approximately 25% and 55% of the administered radioactivity was recovered in the urine and feces, respectively. Less than 1% of unchanged aripiprazole was excreted in the urine and approximately 18% of the oral dose was recovered unchanged in the feces.

The steady-state volume of distribution of aripiprazole following intravenous administration is high (404 L or 4.9 L/kg), indicating extensive extravascular distribution.

The clearance of aripiprazole was estimated to be 0.8mL/min/kg. Other studies have also reported a clearance rate of 3297±1042mL/hr.

Oral availability 87%. Aripiprazole is well absorbed and can be administered with or without food. Administration with a high fat meal did not affect the Cmax or AUC, but delayed Tmax by 3 hours for aripiprazole, and 12 hours for dehydro-aripiprazole.

Time to peak concentration: Peak plasma concentrations: within 3 to 5 hours.

MEDICATION

Antipsychotic Agents

Use (kg; approx.) in Germany (2009): >100

For the treatment of schizophrenia and related psychotic disorders.

7-Hydroxy-3,4-dihydro-2(1H)-quinolinone is refluxed with 1,4-dibromobutane plus K2CO3 in DMF to form the 7-(4-bromobutoxy) derivative which is condensed with 1-(3,4-dichlorophenyl)piperazine to yield the product.

Preparation: Y. Oshiro et al., European Patent Office patent 367141; eidem, United States of America patent 5006528 (1990,1991 both to Otsuka).