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1.
Journal of Southern Medical University ; (12): 328-336, 2019.
Artigo em Chinês | WPRIM | ID: wpr-772058

RESUMO

OBJECTIVE@#To study the effect of CYP2D610 (c.100 C>T) on plasma trough concentrations of metoprolol and its metabolite α-hydroxy metoprolol, blood pressure and heart rate in patients with coronary artery disease.@*METHODS@#The patients with coronary artery disease taking metoprolol tablets (=128) and those taking metoprolol sustained-release tablets (=126) were genotyped for CYP2D610 using Taqman real-time quantitative PCR. The trough concentrations of metoprolol and α-hydroxy metoprolol were determined with UPLC-MS/MS, and the dose-normalized concentrations (C/D) were compared among the patients with different CYP2D610 genotypes in both groups. Resting blood pressure and heart rate were recorded in all the patients when the concentration of metoprolol reached the steady state and were compared among the patients with different genotypes.@*RESULTS@#In patients taking metoprolol sustained-release tablets, the plasma trough concentration of α-hydroxy metoprolol was significantly associated with the systolic blood pressure (=0.0204). The CYP2D610 poor metabolizers showed a significant association with the C/D of metoprolol and α-hydroxy metoprolol ( < 0.01) in patients receiving metoprolol in both formulations, and in both groups, the C/D of metoprolol was significantly higher in the patients with a TT genotype than in those with a CC or CT genotype ( < 0.01); compared with those with the CT genotype, the patients with the TT genotype had a significantly lower C/D of α-hydroxy metoprolol ( < 0.01). In patients taking metoprolol sustained-release tablets, those with the CT (=0.0281) and TT (=0.0196) genotypes had lower diastolic blood pressure than patients with the CC genotypes, but the systolic blood pressure or heart rate did not differ significantly among them.@*CONCLUSIONS@#CYP2D610T allele mutation can reduce the metabolism of metoprolol, increase the C/D of metoprolol and decrease the C/D of α-metoprolol and diastolic blood pressure in patients with coronary artery disease, but CYP2D610 variation does not significantly affect systolic blood pressure or heart rate in the patients when the concentration of metoprolol reaches a steady state.


Assuntos
Humanos , Antagonistas Adrenérgicos beta , Cromatografia Líquida , Doença da Artéria Coronariana , Citocromo P-450 CYP2D6 , Genótipo , Metoprolol , Espectrometria de Massas em Tandem
2.
Korean Journal of Anesthesiology ; : 84-89, 2006.
Artigo em Coreano | WPRIM | ID: wpr-162975

RESUMO

BACKGROUND: Postoperative nausea and vomiting (PONV) are common problems in patients undergoing general anesthesia. Ondansetron is widely used for this problems. But, some patients treated with ondansetron do not respond to therapy. We hypothesized that patients with genetic variation in 5-HT3b receptor and CYP2D6 gene might respond differently to ondansetron treatment. METHODS: 135 patients undergoing gynecologic surgery were given 4 mg ondansetron 15 min before extubation. The assessment of PONV was performed during < 2 hours and 2-24 hours. DNA was extracted from blood and was analyzed by using restriction fragment-length polymorphism (RFLP) and site-specific PCR. RESULTS: In 5-HT3b AAG deletion mutation, the incidence of nausea and vomiting < 2 hr were 25% and 12.5% for wild, 23.4% and 12.2% for heteromutant. The incidence of nausea and vomiting 2-24 hr were 3.2% and 1.1% for wild, 4.9% and 2.4% for heteromutant. This showed no significant differences between two groups. In CYP2D6*10 mutation, the incidence of nausea and vomiting < 2 hr were 28.6% and 19.6% for wild, 22.8% and 8.8% for heteromutant and 23.5% and 5.9% for homomutant. The incidence of nausea and vomiting 2-24 hr were 5.4% and 1.8% for wild, 3.2% and 1.6% for heteromutant, 0% and 0% for homomutant. This showed no significant differences among three groups. CONCLUSIONS: The incidence of PONV were not different among the genotype of CYP2D6*10 and 5HT3b AAG mutation.


Assuntos
Feminino , Humanos , Anestesia Geral , Citocromo P-450 CYP2D6 , DNA , Variação Genética , Genótipo , Procedimentos Cirúrgicos em Ginecologia , Incidência , Náusea , Ondansetron , Reação em Cadeia da Polimerase , Polimorfismo Genético , Náusea e Vômito Pós-Operatórios , Deleção de Sequência , Vômito
3.
Chinese Pharmacological Bulletin ; (12)2003.
Artigo em Chinês | WPRIM | ID: wpr-561868

RESUMO

Aim To establish a new simple, easy and economical PCR method for determining cyp2d6~*10 allele and studying its distributive frequencies in Chinese population. Methods The new PCR are established and compared with the classical PCR-RFLP. The 224 samples have been determined with the new PCR.Results the results of the two methods go on the way. The allele distribution frequencies of cyp2d6~*10 resembles the reports. Conclusion the new method is proved to be accurate and convenient. It provides a genetics basis for the drug therapy with individuals in clinics.

4.
Journal of the Korean Society of Biological Psychiatry ; : 140-146, 2000.
Artigo em Coreano | WPRIM | ID: wpr-724866

RESUMO

P450 CYP2D6 enzyme(debrisoquine hydroxylase) is known to metabolize many neuroleptics and some genetic polymorphisms in the CYP2D6 gene were reported to be associated with tardive dyskinesia(TD). We investigeted the association of two genetic polymorphisms in the CYP2D6 gene, CYP2D6*4 and CYP2D6*10, with TD in Korean schizophrenic subjects. Subjects consisted of 71 Korean schizophrenics and TD was evaluated using the Abnormal Involuntary Movement Scale(AIMS). There were no statistically significant differences in the demographic variables of age, male to female percentage and the current antipsychotic(CPZ equivalent) dose between the grup with TD and the group without TD. But the duration of antipsychotic drug exposure was siginificantly higher in the group without TD(p=0.000, by independent t-test). The mean AIMS score in the group with TD was 11.2+/-6.6(S.D.). Genotypings ofr the presence of CYP2D6*4 and CYP2D6*10 wee done using PCR amplifications and endonuclease digestions. There were no statistically significant genotypic and alleleic associations between TD and CYP2D6*4(by chi-square tests), and between TD and CYP2D6*10(by chi-square tests). These results indicate that the CYP2D6*4 and CYP2D6*10 polymorphisms have no significant roles in the causation of TD.


Assuntos
Feminino , Humanos , Masculino , Antipsicóticos , Povo Asiático , Citocromo P-450 CYP2D6 , Discinesias , Transtornos dos Movimentos , Reação em Cadeia da Polimerase , Polimorfismo Genético
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