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Influence of cytochrome P450 genotype on the plasma disposition of prochlorperazine metabolites and their relationships with clinical responses in cancer patients
- Source :
- Annals of clinical biochemistry. 55(3)
- Publication Year :
- 2017
-
Abstract
- 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 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 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 prochlorperazine metabolites did not have a strong effect on antiemetic efficacy, while they were slightly associated with prolactin secretion in cancer patients.
- Subjects :
- Male
Cytochrome
Genotype
Clinical Biochemistry
Pharmacology
030226 pharmacology & pharmacy
Prochlorperazine
03 medical and health sciences
0302 clinical medicine
Cytochrome P-450 Enzyme System
Dopamine receptor D2
Neoplasms
medicine
Humans
Aged
biology
business.industry
Antagonist
Cytochrome P450
Cancer
General Medicine
Middle Aged
medicine.disease
Prolactin
030220 oncology & carcinogenesis
biology.protein
Antiemetics
Dopamine Antagonists
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 17581001
- Volume :
- 55
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Annals of clinical biochemistry
- Accession number :
- edsair.doi.dedup.....3d53eed9eb22386ca5d97abd11523cdc