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1. Ann Clin Biochem. 2018 May;55(3):385-393. doi: 10.1177/0004563217731432. Epub </div>
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2017 Oct 12.Influence of cytochrome P450 genotype on the plasma disposition of </div>
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prochlorperazine metabolites and their relationships with clinical responses in </div>
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cancer patients.Tashiro M(1)(2)(3), Naito T(1), Kagawa Y(2), Kawakami J(1).</div>
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Background Oral prochlorperazine, a dopamine D2 receptor antagonist, is largely metabolized to sulphoxide, 7-hydroxylate and N-desmethylate by cytochrome P450s (CYPs). This study evaluated the influence of CYP genotype on the plasma </div>
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dispositions of prochlorperazine and its metabolites and their relationships with antiemetic efficacy and prolactin elevation in cancer patients. Methods Forty-eight cancer patients treated with oral prochlorperazine were enrolled. Plasma prochlorperazine and its metabolites concentrations and serum prolactin concentration were determined at 12 h after the evening dosing. The genotypes of CYP2C19, CYP2D6 and CYP3A5 and the incidences of nausea and vomiting were </div>
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investigated. Results The plasma concentrations of the prochlorperazine metabolites were weakly correlated with that of the parent drug. The CYP genotypes did not affect the plasma concentrations of prochlorperazine and its metabolites. The plasma concentrations of prochlorperazine and its metabolites were not associated with the incidences of nausea and vomiting. The incidence of vomiting was significantly higher in females than in males. The serum prolactin concentration was weakly correlated with the plasma concentrations of prochlorperazine and its metabolites. The plasma concentrations of prochlorperazine metabolites rather than the parent drug had a weaker relation to serum prolactin concentration. Conclusions The CYP genotypes did not affect the plasma dispositions of prochlorperazine and its metabolites. The </div>
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prochlorperazine metabolites did not have a strong effect on antiemetic efficacy, while they were slightly associated with prolactin secretion in cancer patients.</div>
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2. Biomed Chromatogr. 2012 Jun;26(6):754-60. doi: 10.1002/bmc.1725. Epub 2011 Oct 12.Simultaneous determination of prochlorperazine and its metabolites in human plasma using isocratic liquid chromatography tandem mass spectrometry.Tashiro M(1), Naito T, Kagawa Y, Kawakami J.</div>
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Oral prochlorperazine (PCZ), an antiemetic, undergoes extensive first-pass metabolism. The study developed a simultaneous analytical method for PCZ and its major metabolites, prochlorperazine sulfoxide (PCZSO), </div>
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N-demethylprochlorperazine (NDPCZ) and 7-hydroxyprochlorperazine (PCZOH), in human plasma using an isocratic liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Deproteinized plasma specimens were separated using a 3 µm particle size octadecylsilyl column, and the run time was 10 min. The calibration curves were linear over the concentration ranges of 0.01-40 µg/L for PCZ, NDPCZ and PCZOH, and 0.05-80 µg/L for PCZSO. The intra- and inter-assay precisions and accuracies were within 7.0 and 99-104% and within 9.0 and 99-105%, respectively. The lower limits of quantification in human plasma were 10 ng/L for PCZ, NDPCZ and PCZOH, and 50 ng/L for PCZSO. The validated method </div>
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was applied to the determination of plasma samples in 37 cancer patients receiving PCZ. Large interindividual variations were observed in plasma concentrations of PCZ, PCZSO, NDPCZ and PCZOH (relative standard deviation, 89.4, 88.7,86.4 and 78.2%, respectively). In conclusion, this simultaneous LC-MS/MS method with acceptable analytical performance can be helpful for evaluating the pharmacokinetics of PCZ, including the determination of its metabolites in cancer patients and in clinical research.</div>
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3. Biochem Pharmacol. 1974 Jan 15;23(2):303-11. doi: 10.1016/0006-2952(74)90421-3.Metabolism of trifluoperazine, fluphenazine, prochlorperazine and perphenazine in rats: in vitro and urinary metabolites.Gaertner HJ, Breyer U, Liomin G.</div>
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