High performance liquid chromatographic methods for the determination of aripiprazole with ultraviolet detection in rat plasma and brain: Application to the pharmacokinetic study

Shimokawa, Yoshihiko; Akiyama, Hitoshi; Kashiyama, Eiji; Koga, Toshitaka; Miyamoto, Gohachiro

doi:10.1016/j.jchromb.2005.03.024

Cited by 66 publications

(50 citation statements)

References 9 publications

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“…Initial experiments in monkeys responding under an FR schedule of food presentation indicated that the behavioral effects of ARI were present for more than 3 hours but dissipated by 18 hours after administration. This places the half-life of ARI in cynomolgus monkeys clearly between its half-life in humans (∼60 hours; McGavin and Goa, 2002;Mallikaarjun et al, 2004) and rodents (∼2 hours; Shimokawa et al, 2005). Although all three drugs only decreased food-maintained responding under an FR contingency, when tested in a food-cocaine choice paradigm, acute administration of drugs revealed individual-subject variability in sensitivity to the effects of ARI, (2)2NPA, and ETIC, with increases in behavior noted.…”

Section: Discussionmentioning

confidence: 69%

Effects of Dopamine D2/D3 Receptor Ligands on Food-Cocaine Choice in Socially Housed Male Cynomolgus Monkeys

Czoty

Nader

2012

J Pharmacol Exp Ther

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Dopamine D2/D3 receptor partial agonists have been suggested as medications for cocaine dependence. The present experiments examined the effect of acute and repeated administration of drugs with varying intrinsic efficacy at D2/D3 receptors on the relative reinforcing strength of cocaine. Use of socially housed cynomolgus monkeys permitted the assessment of whether social status, known to alter D2/D3 receptor availability, influenced the behavioral effects of D2/D3 receptor compounds. The high-efficacy agonist R(2)2norpropylapomorphine [(2)2NPA], low-efficacy agonist aripiprazole (ARI), and antagonist eticlopride (ETIC) were administered acutely to monkeys self-administering cocaine under a food-cocaine choice procedure in which a cocaine self-administration dose-effect curve was determined daily. The effects of 5-day treatment with ARI and (2)2NPA were characterized under conditions in which monkeys did (ARI) or did not [ARI and (2)2NPA] self-administer cocaine during treatment. When administered acutely, ARI and ETIC increased the choice of low cocaine doses, and only (2)2NPA decreased the choice of higher cocaine doses and cocaine intake; effects were similar across social ranks. When administered repeatedly while self administration occurred only on days 1 and 5 of treatment, ARI, but not (2)2NPA, decreased cocaine choice in dominant monkeys, whereas (2)2NPA, but not ARI, did so in subordinates. When dominant monkeys self-administered cocaine on all five days of ARI treatment, however, these effects were not observed. The results indicate that the behavioral effects of D2/D3 receptor agonists can differ according to intrinsic efficacy and subject characteristics. Moreover, these results suggest that exposure to cocaine during treatment can counteract treatment-induced reductions in the reinforcing effects of cocaine.

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Section: Discussionmentioning

confidence: 69%

Effects of Dopamine D2/D3 Receptor Ligands on Food-Cocaine Choice in Socially Housed Male Cynomolgus Monkeys

Czoty

Nader

2012

J Pharmacol Exp Ther

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“…In the previously published papers, the chromatographic behavior of aripiprazole was investigated on the octadecyl [3, 4, 22-24, 27, 28], octyl [7,25] or phenyl [6,26] chemically bonded stationary phases using the isocratic [22][23][24][25][26], and the gradient [27,28] elution modes. Recently, a significant improvement was obtained with the quality of the HPLC-type chemically bonded silica particles, which resulted in an increased number of the available RP columns with different functionalities and selectivity.…”

Section: Resultsmentioning

confidence: 99%

“…In both human and animal samples, concentration of aripiprazole was determined alone, or simultaneously with its main metabolite, dehydroaripiprazole. The levels were measured using high-performance liquid chromatography (HPLC) with UV detection [3][4][5][6][7]; capillary-electrophoresis [7][8][9]; and HPLC, ultraperformance liquid chromatography (UPLC), or gas chromatograph (GC) coupled with mass spectrometry [10][11][12][13][14][15][16][17]. Three biotransformation pathways were identified after oral administration of 14 C-labeled aripiprazole: dehydrogenation, N-dealkylation, and hydroxylation.…”

Section: Introductionmentioning

confidence: 99%

Validation of an HPLC method for determination of aripiprazole and its impurities in pharmaceuticals

Filijović¹,

Pavlović²,

Nikolić³

et al. 2014

Acta Chromatographica

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Summary.Aripiprazole is a novel atypical antipsychotic drug used in the treatment of schizophrenia. The sensitive and reproducible ion pair RPLC method was developed and validated for determination of aripiprazole and its nine impurities, which are significantly different in polarity. The separation was performed on Phenomenex Luna ® C18 column (5.0 μm particle size, 250 × 4.6 mm id) using a gradient mobile phase A (phosphate buffer pH 3.0) and mobile phase B (acetonitrile) at the working temperature of 25°C. The buffer was 1.11 g KH 2 PO 4 with 1.2 g sodium pentanesulfonate/L of the solution, adjusted to pH 3.0 with orthophosphoric acid. The flow rate was 1.0 mL/min. The detection was carried out at 215 nm using a diode array detector. The developed method was validated according to the International Conference on Harmonization (ICH) guidelines for specificity, limit of detection, limit of quantification, linearity, precision and robustness. The proposed method is convenient and reliable for the purity control in both raw materials and dosage forms.

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“…Haloperidol's plasma half-life is 14.5-36.7 hours in humans (de Leon et al, 2004), but 1.5 hours in rats (Cheng and Paalzow, 1992). Aripiprazole has a long plasma elimination half-life (60-70 hours) in humans (Grunder et al, 2008), while in rats aripiprazole reached the maximal plasma concentration (C max ) 2 hours after oral administration (10mg/kg) with an elimination half-life of 2.2 hours (Shimokawa et al, 2005). Therefore, all rats were treated three times per day, at 06:00, 14:00, and 22:00 h, orally by administering specially prepared sweet cookie dough pellets (0.3g) to ensure a consistently high concentration to better mirror the human scenario of oral administration once per day (Deng et al, 2012;Han et al, 2008;Weston-Green et al, 2011).…”

Section: Animals and Drug Treatmentmentioning

confidence: 99%

Differential effects of short- and long-term antipsychotic treatment on the expression of neuregulin-1 and ErbB4 receptors in the rat brain

Deng

Pan

et al. 2015

Psychiatry Research

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Neuregulin-1 (NRG1) and ErbB4 genes have been identified as candidate genes for schizophrenia. Postmortem studies indicated that NRG1-ErbB4 signalling is impaired in schizophrenia subjects. This study investigated whether short-or long-term antipsychotic treatment has different effects on the expression of NRG1 and ErbB4 receptors. Female Sprague-Dawley rats were treated orally with either aripiprazole (0.75 mg/kg), haloperidol (0.1 mg/kg), olanzapine (0.5 mg/kg), or vehicle, 3 times/day for 1 or 12 weeks. Western blotting was performed to examine the expression of NRG1 isoforms (135 kDa, 70 kDa and 40 kDa) and ErbB4 receptors. Both 1-week haloperidol and olanzapine treatment increased NRG1-70 kDa expression in the hippocampus; haloperidol also up-regulated ErbB4 levels in the prefrontal cortex (PFC). In the 12-week group, aripiprazole decreased the expression of all three NRG1 isoforms and ErbB4 receptors in the PFC, NRG1-70 kDa and -40 kDa in the cingulate cortex (Cg), and NRG1-135 kDa, -70 kDa and ErbB4 receptors in the hippocampus; haloperidol reduced NRG1-135 kDa in the PFC, NRG1-40 kDa in all three brain regions, and ErbB4 receptor levels in the PFC and hippocampus; NRG1-40 kDa in the PFC and Cg was also downregulated by olanzapine. These results suggest that the time-dependent and region-specific effects of antipsychotics on NRG1-ErbB4 signalling may contribute to the efficacy of antipsychotics to treat schizophrenia. AbstractNeuregulin-1 (NRG1) and ErbB4 genes have been identified as candidate genes for schizophrenia. Post-mortem studies indicated that NRG1-ErbB4 signalling is impaired in schizophrenia subjects. This study investigated whether short-or long-term antipsychotic treatment has different effects on the expression of NRG1 and ErbB4 receptors. Female Sprague-Dawley rats were treated orally with either aripiprazole (0.75mg/kg), haloperidol (0.1mg/kg), olanzapine (0.5mg/kg), or vehicle, 3 times/day for 1 or 12 weeks. Western blotting was performed to examine the expression of NRG1 isoforms (135kDa, 70kDa and 40kDa) and ErbB4 receptors. Both 1-week haloperidol and olanzapine treatment increased NRG1-70kDa expression in the hippocampus; haloperidol also up-regulated ErbB4 levels in the prefrontal cortex (PFC). In the 12-week group, aripiprazole decreased the expression of all three NRG1 isoforms and ErbB4 receptors in the PFC, NRG1-70kDa and -40kDa in the cingulate cortex (Cg), and NRG1-135kDa, -70kDa and ErbB4 receptors in the hippocampus; haloperidol reduced NRG1-135kDa in the PFC, NRG1-40kDa in all three brain regions, and ErbB4 receptor levels in the PFC and hippocampus; NRG1-40kDa in the PFC and Cg was also down-regulated by olanzapine. These results suggest that the time-dependent and regionspecific effects of antipsychotics on NRG1-ErbB4 signalling may contribute to the efficacy of antipsychotics to treat schizophrenia.

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High performance liquid chromatographic methods for the determination of aripiprazole with ultraviolet detection in rat plasma and brain: Application to the pharmacokinetic study

Cited by 66 publications

References 9 publications

Effects of Dopamine D2/D3 Receptor Ligands on Food-Cocaine Choice in Socially Housed Male Cynomolgus Monkeys

Effects of Dopamine D2/D3 Receptor Ligands on Food-Cocaine Choice in Socially Housed Male Cynomolgus Monkeys

Validation of an HPLC method for determination of aripiprazole and its impurities in pharmaceuticals

Differential effects of short- and long-term antipsychotic treatment on the expression of neuregulin-1 and ErbB4 receptors in the rat brain

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