The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor

Jordan, Scott W.; Koprivica, Vuk; Chen, Ruoyan; Tottori, Katsura; Kikuchi, Tetsuro; Altar, C. Anthony

doi:10.1016/s0014-2999(02)01532-7

Cited by 481 publications

(254 citation statements)

References 11 publications

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“…Blood samples were collected at 1, 2, 3, 4, 6, 8, and 12 h after the first dose on Day 1, at predose on Day 2-7, at 1, 2, 3, 4, 6, 8, and 12 h after the dose on Day 7, and at predose on Day 8-14. After the last dose on Day 14, blood samples were collected at 1, 2, 3, 4,6,8,12,24,48,72,96,120,168,216, and 288 h. In the protocol-3 trial, each subject first received a single dose of aripiprazole alone at 3 mg once under a fasting condition. After a 5-week washout period, the subjects were administrated itraconazole at 100 mg once daily for 21 consecutive days.…”

Section: Pharmacokinetic Datamentioning

confidence: 99%

“…1,2) The action of aripiprazole is different from that of other typical and atypical antipsychotics; that is, aripiprazole is a potent partial agonist at dopamine D2 and serotonin (5-HT 1A ) receptors and antagonist at 5-HT 2A receptor. 3,4) The results of in vitro studies indicated that aripiprazole is mainly metabolized by human cytochrome P450 isozymes CYP3A4 and CYP2D6.…”

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confidence: 99%

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Nonlinear Mixed Effects Model Analysis of the Pharmacokinetics of Aripiprazole in Healthy Japanese Males

Koue

Kubo

Funaki

et al. 2007

Biological & Pharmaceutical Bulletin

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Aripiprazole is a new antipsychotic developed in Japan, and is prescribed for schizophrenia as a dopamine-serotonin system stabilizer.1,2) The action of aripiprazole is different from that of other typical and atypical antipsychotics; that is, aripiprazole is a potent partial agonist at dopamine D2 and serotonin (5-HT 1A ) receptors and antagonist at 5-HT 2A receptor.3,4) The results of in vitro studies indicated that aripiprazole is mainly metabolized by human cytochrome P450 isozymes CYP3A4 and CYP2D6.5) It has been reported that CYP3A4 and CYP2D6 are metabolic enzymes for numerous compounds, and also that there are many compounds that inhibit these enzymes. Although individual differences in hepatic levels of CYP3A4 enzyme protein have been reported to vary as much as 40-fold, 6) almost no gene mutations affecting CYP3A4 metabolic activity or ethnic differences have been reported. For CYP2D6, however, a number of polymorphisms and the existence of ethnic differences in the types and distribution of polymorphisms have been reported.6,7) The purpose of the present study was to estimate the population pharmacokinetic parameters of aripiprazole in healthy Japanese males, and to evaluate the effects of CYP2D6 polymorphisms and CYP3A4 inhibition on the pharmacokinetics of aripiprazole, and also its unknown (residual) interindividual variability.In the present study, we used the nonlinear mixed-effects model (NONMEM) method designed for the estimation of population pharmacokinetic parameters.8) This method pools data from all individuals but explicitly models and handles the complicated error structure arising from proper accounting of interindividual (h) and intraindividual (e) random effects. The first-order estimation method is the first estimation method available with NONMEM: it handles the error structure of data using first-order Taylor-series expansion in the random effect h, evaluated at the expected values (i.e. hϭ0).9) On the other hand, a newer analysis method designed for the estimation of population parameters, the firstorder conditional estimation (FOCE) method, is available with NONMEM software. 9) That is, FOCE uses first-order expansions for values of the h, but these values are the conditional (Bayesian) estimates of the h, rather than zero. The FOCE method needs much (20-40-fold) longer computational time than the first-order method, but generally gives precise parameter estimates, especially for the analysis of multiple-dose pharmacokinetic data with multiple compartment models. [9][10][11][12] In the present study, therefore, we used the FOCE method to estimate the population pharmacokinetic parameters of aripiprazole, where a two-compartment model with first-order input was applied for data obtained from single-and multiple-dose clinical trials. MATERIALS AND METHODS Pharmacokinetic DataPlasma aripiprazole concentration data for population pharmacokinetic analysis were obtained in two previous studies. 13,14) Briefly, 68 healthy Japanese male subjects, aged 20-32 years old (mean: 23.1) and w...

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Section: Pharmacokinetic Datamentioning

confidence: 99%

mentioning

confidence: 99%

Nonlinear Mixed Effects Model Analysis of the Pharmacokinetics of Aripiprazole in Healthy Japanese Males

Koue

Kubo

Funaki

et al. 2007

Biological & Pharmaceutical Bulletin

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“…Aripiprazole is a novel agent that differs in mechanism of action from every other available antipsychotic drug (Shapiro et al 2003). The compound is a partial D2 and 5-HT1A agonist, and a 5-HT2A antagonist (Burris et al 2002;Jordan et al 2002). Aripiprazole's unique pharmacology may underlie its efficacy in the treatment of a number of disorders as indicated by FDA approvals, including for irritability associated with autistic disorder in children and adolescents.…”

Section: Introductionmentioning

confidence: 99%

A prospective open-label study of aripiprazole in fragile X syndrome

et al. 2011

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“…It is a novel and a typical drug used for the treatment of schizophrenia which is the common and well recognized psychiatric disorder, stimulated by inordinate neurotransmission action of the dopaminergic nervous system in the central nervous system [1]. Aripiprazole is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), dopamine Type 2 (D2) [2], 1 and 2 adrenergic and H1 histaminergic receptors [3,4]. It acts as an antagonist at other receptors but with lower potency.…”

Section: Introductionmentioning

confidence: 99%

Identification of degradation products in Aripiprazole tablets by LC-QToF mass spectrometry

et al. 2010

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KEYWORDSThis paper describes the separation, identification and proposed structures of the degradation products formed during degradation analysis of aripiprazole in its final dosage form by high performance liquid chromatography (HPLC) coupled with quadrupole time-offlight mass spectrometry (QToF-MS). The drug product was subjected to stress conditions including acid, base, thermal, oxidation, humidity and photolytic degradations. Aripiprazole was found to be stable in all conditions except in thermal and peroxide degradations. The degradation impurities were first separated by HPLC and then identified using QToF mass spectrometry. QToF mass spectrometer provided high order of mass accuracy for unknown impurities and their fragment ions to explore the elemental composition. Based on the fragmentation pattern, the possible structures of the unknown impurities were proposed. To the best of our knowledge, there were no methods available to identify the impurities during degradation of aripiprazole tablets by liquid chromatography-mass spectrometry. Aripiprazole Identification of degradation impurities LC-QToF-MS HPLC

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The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor

Cited by 481 publications

References 11 publications

Nonlinear Mixed Effects Model Analysis of the Pharmacokinetics of Aripiprazole in Healthy Japanese Males

Nonlinear Mixed Effects Model Analysis of the Pharmacokinetics of Aripiprazole in Healthy Japanese Males

A prospective open-label study of aripiprazole in fragile X syndrome

Identification of degradation products in Aripiprazole tablets by LC-QToF mass spectrometry

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