Iloperidone

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Nervous system -> Antipsychotics

White to off-white finely crystalline powder

Crystals from ethanol

Practically insoluble in water

Very slightly soluble in 0.1 N HCl; freely soluble in chloroform, ethanol, methanol, acetonitrile

Breast Feeding; Lactation; Milk, Human; Antipsychotic Agents

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Danger

H300 (88.4%): Fatal if swallowed [Danger Acute toxicity, oral]

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

Aggregated GHS information provided per 43 reports by companies from 5 notifications to the ECHA C&L Inventory.

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

Accidental release measures: After Inhalation: cordon off area of spill; wear self-contained breathing apparatus, protective clothing and heavy rubber gloves. Measures for cleaning/collecting absorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); decontaminate surfaces and equipment by scrubbing with alcohol; dispose of contaminated material /in accordance with prevailing country, fededral, state and local regulations/.

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.

Handling should only be performed by personnel trained and familiar with handling of potent active pharmaceutical ingredients.

Information for safe handling: avoid inhalation and contact with skin, eyes and clothing ... .

Because disruption of body temperature regulation is possible, iloperidone should be used with caution in patients concurrently receiving drugs with anticholinergic activity.

Because of additive effects on QT-interval prolongation, concomitant use of iloperidone with other drugs known to prolong the corrected QT (QTc) interval, including class IA antiarrhythmics (e.g., quinidine, procainamide), class III antiarrhythmics (e.g., amiodarone, sotalol), some antipsychotic agents (e.g., chlorpromazine, thioridazine, haloperidol, asenapine, olanzapine, paliperidone, pimozide, quetiapine, ziprasidone), some anti-infective agents (e.g., gatifloxacin, moxifloxacin), and other drugs (e.g., levomethadyl acetate (no longer commercially available in the US), methadone, pentamidine, tetrabenazine), should be avoided.

Concomitant use of iloperidone with other CNS agents or alcohol may produce additive CNS effects. Caution is advised when iloperidone and other CNS agents are used concomitantly; use of alcohol during iloperidone therapy should be avoided.

Because of its alpha1-adrenergic blocking activity and potential to cause orthostatic hypotension and syncope, the manufacturer recommends that iloperidone be used with caution in patients receiving antihypertensive agents and other drugs that can cause hypotension; monitoring of orthostatic vital signs should be considered in such patients.

For more Interactions (Complete) data for Iloperidone (13 total), please visit the HSDB record page.

Liver test abnormalities occur in 1% to 3% of patients on long term therapy with iloperidone, but similar rates are reported with placebo therapy and with comparator agents. The ALT elevations are usually mild, transient and usually resolve even without dose modification or drug discontinuation. There have been no published reports of clinically apparent liver injury with symptoms or jaundice attributed to iloperidone therapy.

IDENTIFICATION AND USE: Ilperidone is a white to off-white finely crystalline powder formulated into oral tablets. Iloperidone is considered an atypical or second-generation antipsychotic agent. It is used for the treatment of adults with schizophrenia. HUMAN EXPOSURE AND TOXICITY: In premarketing trials involving over 3210 patients, accidental or intentional overdose of iloperidone was documented in 8 patients with no fatalities. In general, reported signs and symptoms were those resulting from an exaggeration of the known pharmacological effects (e.g., drowsiness and sedation, tachycardia and hypotension). Elderly patients with dementia-related psychosis treated with iloperidone are at an increased risk of death and therefore iloperidone is not approved for use in that population. Iloperidone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including iloperidone. Hyperglycemia, sometimes severe and associated with ketoacidosis, hyperosmolar coma, or death, has also been reported in patients receiving atypical antipsychotic agents, including iloperidone. Iloperidone has two predominate metabolites, P88 and P95. The P88 metabolite penetrates the CNS and is thought to contribute to the drug's antipsychotic activity whereas the P95 metabolite does not readily penetrate the CNS and primarily contributes to the adverse effect profile of the drug. ANIMAL STUDIES: Lifetime carcinogenicity studies were conducted in mice and rats. Iloperidone was administered orally at doses of 2.5, 5.0, and 10 mg/kg/day to mice and up to 16 mg/kg/day to rats. There was an increased incidence of malignant mammary gland tumors in female mice treated with the lowest dose (2.5 mg/kg/day) only. There were no treatment-related increases in neoplasia in rats. The carcinogenic potential of iloperidone metabolite P95 was studied in rats at oral doses up to 200 mg/kg/day in males and up to 250 mg/kg/day in females. Drug-related neoplastic changes occurred in the pituitary gland (pars distalis adenoma) and in the pancreas (islet cell adenoma). Iloperidone also caused developmental toxicity, but was not teratogenic in rats and rabbits. Pregnant rats were given up to 64 mg/kg/day of iloperidone during the period of organogenesis. The highest dose caused increased early intrauterine deaths and decreased fetal viability at term; this dose also caused maternal toxicity. In a similar study, pregnant rabbits were given up to 25 mg/kg of iloperidone during the period of organogenesis. The highest dose caused increased early intrauterine deaths and decreased fetal viability at term; this dose also caused maternal toxicity. Additional studies in rats given iloperidone either pre-conception or from day 17 of gestation and continuing through weaning caused adverse reproductive effects including prolonged pregnancy and parturition, increased stillbirth rates, increased incidence of fetal visceral variations, decreased fetal and pup weights, and decreased post-partum pup survival. There were no drug effects on the neurobehavioral or reproductive development of the surviving pups. Iloperidone decreased fertility at 12 and 36 mg/kg in a study in which both male and female rats were treated. Iloperidone was negative in the Ames test and in the in vivo mouse bone marrow and rat liver micronucleus tests. Iloperidone induced chromosomal aberrations in Chinese Hamster Ovary (CHO) cells in vitro at concentrations which also caused some cytotoxicity.

/SIGNS AND SYMPTOMS/ Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. Fanapt should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

/SIGNS AND SYMPTOMS/ Geriatric patients with dementia-related psychosis treated with iloperidone are at an increased risk of death compared with those receiving placebo. In addition, an increased incidence of adverse cerebrovascular events (cerebrovascular accidents and transient ischemic attacks), including fatalities, has been observed in geriatric patients with dementia-related psychosis treated with certain atypical antipsychotic agents (aripiprazole, olanzapine, risperidone) in placebo-controlled studies. The manufacturer states that the safety and efficacy of iloperidone in the treatment of psychosis associated with Alzheimer's disease have not been established and that the drug is not approved for the treatment of patients with dementia-related psychosis. If a clinician decides to treat such patients with iloperidone, the manufacturer recommends that vigilance be exercised.

/SIGNS AND SYMPTOMS/ In premarketing trials involving over 3210 patients, accidental or intentional overdose of Fanapt was documented in 8 patients ranging from 48 mg to 576 mg taken at once and 292 mg taken over a 3-day period. No fatalities were reported from these cases. The largest confirmed single ingestion of Fanapt was 576 mg; no adverse physical effects were noted for this patient. The next largest confirmed ingestion of Fanapt was 438 mg over a 4-day period; extrapyramidal symptoms and a QTc interval of 507 msec were reported for this patient with no cardiac sequelae. This patient resumed Fanapt treatment for an additional 11 months. In general, reported signs and symptoms were those resulting from an exaggeration of the known pharmacological effects (e.g., drowsiness and sedation, tachycardia and hypotension) of Fanapt.

/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 Fanapt. Clinical manifestations include hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs) 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.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Iloperidone

Ambiguous-DILI-concern

2

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The carcinogenic potential of the iloperidone metabolite P95, which is a major circulating metabolite of iloperidone in humans but is not present at significant amounts in mice or rats, was assessed in a lifetime carcinogenicity study in Wistar rats at oral doses of 25, 75, and 200 mg/kg/day in males and 50, 150, and 250 (reduced from 400) mg/kg/day in females. Drug-related neoplastic changes occurred in males, in the pituitary gland (pars distalis adenoma) at all doses and in the pancreas (islet cell adenoma) at the high dose. Plasma levels of P95 (AUC) in males at the tested doses (25, 75, and 200 mg/kg/day) were approximately 0.4, 3, and 23 times, respectively, the human exposure to P95 at the maximum recommended human dose (MRHD) of iloperidone. An increase in mammary, pituitary and endocrine pancreas neoplasms has been found in rodents after chronic administration of other antipsychotic drugs and is considered to be mediated by prolonged dopamine D2 antagonism and hyperprolactinemia. Increases in serum prolactin were seen in mice and rats treated with iloperidone. The relevance of these tumor findings in rodents in terms of human risk is unknown. /Iloperidone metabolite (P95)/

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Lifetime carcinogenicity studies were conducted in CD-1 mice and Sprague Dawley rats. Iloperidone was administered orally at doses of 2.5, 5.0, and 10 mg/kg/day to CD-1 mice and 4, 8, and 16 mg/kg/day to Sprague Dawley rats (0.5, 1.0, and 2.0 times and 1.6, 3.2, and 6.5 times, respectively, the maximum recommended human dose (MRHD) of 24 mg/day on a mg/sq m basis). There was an increased incidence of malignant mammary gland tumors in female mice treated with the lowest dose (2.5 mg/kg/day) only. There were no treatment-related increases in neoplasia in rats.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Iloperidone decreased fertility at 12 and 36 mg/kg in a study in which both male and female rats were treated. The no-effect dose was 4 mg/kg, which is 1.6 times the maximum recommended human dose (MRHD) of 24 mg/day on a mg/sq m basis.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In additional studies in which ... rats .. were given iloperidone ... beginning from either pre-conception or from day 17 of gestation and continuing through weaning, adverse reproductive effects included prolonged pregnancy and parturition, increased stillbirth rates, increased incidence of fetal visceral variations, decreased fetal and pup weights, and decreased post-partum pup survival. There were no drug effects on the neurobehavioral or reproductive development of the surviving pups. No-effect doses ranged from 4 to 12 mg/kg except for the increase in stillbirth rates which occurred at the lowest dose tested of 4 mg/kg, which is 1.6 times the maximum recommended human dose (MRHD) on a mg/sq m basis. Maternal toxicity was seen at the higher doses in these studies.

For more Non-Human Toxicity Excerpts (Complete) data for Iloperidone (8 total), please visit the HSDB record page.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analysis of seventeen placebo-controlled trials (modal duration 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Fanapt is not approved for the treatment of patients with dementia-related psychosis.

Iloperidone is not recommended in patients with any degree of hepatic impairment.

Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. Fanapt should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Emergency and supportive measures: 1. Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. 2. Treat coma, seizures, hypotension, and hyperthermia if they occur. 3. Monitor vital signs ECG for at least 6 hours and admit the patient for at least 24 hours if there are signs of significant intoxication. Children with antipsychotic intoxication should be evaluated for possible intentional abuse. /Antipsychotic drugs/

Specific drugs and antidotes. There is no specific antidote.1. Dystonic reactions. Give diphenhydramine ... or benztropine ... . 2. QRS interval prolongation: treat quinidine-like cardiotoxic effects with bicarbonate ... . 3. Hypotension from these drugs probably involves vasodilation caused by alpha-1 receptor blockade. Treat with iv fluids and, if needed a vasoconstrictor such as norepinephrine or phenylephrine. Theoretically, drugs with beta-2 activity (eg, epinephrine, isoproterenol) may worsen hypotension. 4. QT prolongation and torsade may respond to magnesium infusion or overdrive pacing. /Antipsychotic drugs/

Decontamination. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. /Antipsychotic drugs/

Enhanced elimination. Owing to extensive tissue distribution, these drugs are not effectively removed by dialysis or hemoperfusion. Repeat-dose activated charcoal has not been evaluated. /Antipsychotic drugs/

For more Antidote and Emergency Treatment (Complete) data for Iloperidone (8 total), please visit the HSDB record page.

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

N - Nervous system

QN - Nervous system

Iloperidone binds to various receptors. It exhibits the highest affinity for dopamine D2 receptors, serotonin 5-HT_2A receptors, and α1-adrenergic receptors. Due to its α1 adrenergic antagonism, iloperidone may produce hypotension. It can also prolong the QTc interval.

The exact mechanism of action of iloperidone in schizophrenia and bipolar I disorder has not been fully elucidated. It is believed that the drug mechanism of action may be related to its antagonism at the dopamine D2 and 5-HT2A receptors.

Iloperidone is a piperidinyl-benzisoxazole derivative structurally related to risperidone; the drug has been referred to as an atypical or second-generation antipsychotic agent. Although the exact mechanism of action of iloperidone and other antipsychotic agents in schizophrenia is unknown, it has been suggested that the efficacy of iloperidone is mediated through a combination of antagonist activity at central dopamine type 2 (D2) and serotonin type 2 (5-hydroxytryptamine (5-HT2)) receptors.

Fanapt exhibits high (nM) affinity binding to serotonin 5-HT2A dopamine D2 and D3 receptors, and norepinephrine NEalpha1 receptors (Ki values of 5.6, 6.3, 7.1, and 0.36 nM, respectively). FANAPT has moderate affinity for dopamine D4, and serotonin 5-HT6 and 5-HT7 receptors (Ki values of 25, 43, and 22, nM respectively), and low affinity for the serotonin 5-HT1A, dopamine D1, and histamine H1 receptors (Ki values of 168, 216 and 437 nM, respectively). Fanapt has no appreciable affinity (Ki >1000 nM) for cholinergic muscarinic receptors. Fanapt functions as an antagonist at the dopamine D2, D3, serotonin 5-HT1A and norepinephrine alpha1/alpha2C receptors. The affinity of the FANAPT metabolite P88 is generally equal or less than that of the parent compound. In contrast, the metabolite P95 only shows affinity for 5-HT2A (Ki value of 3.91) and the NEalpha1A, NEalpha1B, NEalpha1D, and NEalpha2C receptors (Ki values of 4.7, 2.7, 8.8, and 4.7 nM respectively).

Iloperidone has demonstrated an interesting monoamine receptor profile in radioligand binding studies, with nanomolar affinity for certain noradrenaline, dopamine, and serotonin receptors. In this study, the agonist/antagonist activity of iloperidone was determined in cell lines expressing recombinant human D(2A), D(3), alpha(2C), 5-HT(1A), or 5-HT(6) receptors. With the exception of 5-HT(6) receptors, these receptors are negatively coupled to cyclase. Thus, after stimulation with forskolin, the agonists dopamine (at D(2A) and D(3)), noradrenaline (at alpha(2C)), or 8-OH-DPAT (at 5-HT(1A)) induced a reduction in cAMP accumulation. Conversely, activation of the 5-HT(6) receptor by 5-HT led to an increase in cAMP accumulation. Iloperidone alone was devoid of significant agonist activity but inhibited the agonist response in all 5 cell lines in a surmountable and concentration-dependent fashion. Iloperidone was most potent at D(3) receptors (pK(B) 8.59 + or - 0.20; n = 6), followed by alpha(2C) (pK(B) 7.83 + or - 0.06; n = 15), 5-HT(1A) (pK(B) 7.69 + or - 0.18; n = 10), D(2A) (pK(B) 7.53 + or - 0.04; n = 11) and 5-HT(6) (pK(B) 7.11 + or - 0.08; n = 11) receptors.

Iloperidone ... demonstrated a potent antipsychotic profile in several in vitro and in vivo animal models. Iloperidone displaced ligand binding at D2 dopamine receptors (IC50 = 0.11 uM) and displayed a high affinity for serotonin (5-HT2) receptors (IC50 = 0.011 uM) and alpha-1 receptors (IC50 = 0.00037 uM). ...

The observed mean elimination half-lives for iloperidone, P88, and P95 in CYP2D6 extensive metabolizers (EM) are 18, 26, and 23 hours, respectively. The mean half-lives of iloperidone, P88, and P95 in CYP2D6 poor metabolizers (PM) are 33, 37, and 31 hours, respectively.

The mean elimination half-lives of iloperidone, P88, and P95 are 18, 26, and 23 hours, respectively, in extensive metabolizers of CYP2D6 and 33, 37, and 31 hours, respectively, in poor metabolizers of CYP2D6.

Iloperidone is mainly metabolized in the liver. It primarily undergoes three major biotransformation pathways: carbonyl reduction to produce P88, CYP2D6-mediated hydroxylation to produce P95, and CYP3A4-mediated O-demethylation to produce P89. P88 and P95 are the two major metabolites. P95 represents 47.9% of the AUC of iloperidone and its metabolites in plasma at steady-state for extensive metabolizers (EM) and 25% for poor metabolizers (PM). P88 is an active metabolite with an in vitro receptor binding profile that is comparable to the parent drug: It accounts for 19.5% and 34% of total plasma exposure in EM and PM, respectively.

Iloperidone is primarily metabolized by carbonyl reduction, cytochrome P-450 (CYP) isoenzyme 2D6-mediated hydroxylation, and CYP3A4-mediated O-demethylation; the drug's two principal metabolites, P88 and P95, undergo further oxidation and/or conjugation with glucuronic acid. The P88 metabolite penetrates the CNS and is thought to contribute to the drug's antipsychotic activity whereas the P95 metabolite does not readily penetrate the CNS and primarily contributes to the adverse effect profile of the drug.

Iloperidone is metabolized primarily by 3 biotransformation pathways: carbonyl reduction, hydroxylation (mediated by CYP2D6) and O-demethylation (mediated by CYP3A4). There are 2 predominant iloperidone metabolites, P95 and P88. The iloperidone metabolite P95 represents 47.9% of the AUC of iloperidone and its metabolites in plasma at steady-state for extensive metabolizers (EM) and 25% for poor metabolizers (PM). The active metabolite P88 accounts for 19.5% and 34.0% of total plasma exposure in EM and PM, respectively. Approximately 7% to 10% of Caucasians and 3% to 8% of black/African Americans lack the capacity to metabolize CYP2D6 substrates and are classified as poor metabolizers (PM), whereas the rest are intermediate, extensive or ultrarapid metabolizers. Co-administration of Fanapt with known strong inhibitors of CYP2D6 like fluoxetine results in a 2.3-fold increase in iloperidone plasma exposure, and therefore one-half of the Fanapt dose should be administered. Similarly, PMs of CYP2D6 have higher exposure to iloperidone compared with EMs and PMs should have their dose reduced by one-half.

Iloperidone has known human metabolites that include 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]-2-hydroxyethanone, 4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxy-a-methylbenzene methanol, and 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]- propoxy]-3-hydroxyphenyl]ethanone.

VPO7KJ050N

ILOPERIDONE

Established Pharmacologic Class [EPC] - Atypical Antipsychotic

Iloperidone is an Atypical Antipsychotic.

ILOPERIDONE

Atypical Antipsychotic [EPC]

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.

Iloperidone is well-absorbed following oral administration. Oral bioavailability is approximately 36% in humans. The relative availability of the tablet formulation compared to the oral solution is 96%. The Tmax is two to four hours with single dosing and 1.5 hours with multiple dosing. A high-fat meal can delay the Tmax of iloperidone and its active metabolite, P88, by one and two hours, respectively; however, food has negligible effects on drug Cmax and AUC.

The main route of elimination is renal. About 58.2% and 45.1% of the drug were found in urine in extensive metabolizers (EM) and poor metabolizers (PM), respectively. Feces accounted for 19.9% (EM) to 22.1% (PM) of the dosed radioactivity.

The apparent volume of distribution ranges from 1340 L to 2800 L.

Iloperidone has an apparent clearance of 47 to 102 L/h.

Iloperidone has an apparent clearance (clearance/bioavailability) of 47 to 102 L/hr, with an apparent volume of distribution of 1340 to 2800 L. At therapeutic concentrations, the unbound fraction of iloperidone in plasma is approximately 3% and of each metabolite (P88 and P95) it is approximately 8%.

The majority of radiolabeled iloperidone was recovered in the urine (mean 58.2% and 45.1% in extensive and poor metabolizers of CYP2D6, respectively), with feces accounting for 19.9% (extensive metabolizers) and 22.1% (poor metabolizers) of the radiolabeled dose.

MEDICATION

An atypical, negative symptom antipsychotic agent.