Change From the CYP2D6 Extensive Metabolizer to the Poor Metabolizer Phenotype During Treatment With Bupropion

2002 ◽  
Vol 24 (3) ◽  
pp. 436-437 ◽  
Author(s):  
Cüneyt Güzey ◽  
Åke Norström ◽  
Olav Spigset
2021 ◽  
Vol 12 ◽  
Author(s):  
Xinyi Huang ◽  
Chao Li ◽  
Chaopeng Li ◽  
Zhenyu Li ◽  
Xiaohui Li ◽  
...  

Depression disorder is one of the most serious mental illnesses in the world. Escitalopram is the essential first-line medication for depression disorder. It is the substrate of hepatic cytochrome P450 (CYP) enzyme CYP2C19 with high polymorphism. The effect of CYP2C19 on pharmacokinetics and pharmacodynamics on Caucasian population has been studied. The Clinical Pharmacogenetics Implementation Consortium Guideline provides dosing recommendations for escitalopram on CYP2C19 genotypes on the basis of the studies on Caucasian population. However, the gene frequency of the alleles of CYP2C19 showed racial differences between Chinese and Caucasian populations. Representatively, the frequency of the *2 and *3 allele, which were considered as poor metabolizer, has been shown to be three times higher in Chinese than in Caucasians. In addition, the environments might also lead to different degrees of impacts on genotypes. Therefore, the guidelines based on the Caucasians may not be applicable to the Chinese, which induced the establishment of a guideline in China. It is necessary to provide the evidence of individual treatment of escitalopram in Chinese by studying the effect of CYP2C19 genotypes on the pharmacokinetics parameters and steady-state concentration on Chinese. In this study, single-center, randomized, open-label, two-period, two-treatment crossover studies were performed. Ninety healthy Chinese subjects finished the trials, and they were included in the statistical analysis. The pharmacokinetics characteristics of different genotypes in Chinese were obtained. The results indicate that the poor metabolizer had higher exposure, and increased half-life than the extensive metabolizer and intermediate metabolite. The prediction of steady-state concentration based on the single dose trial on escitalopram shows that the poor metabolizer might have a higher steady-state concentration than the extensive metabolizer and intermediate metabolite in Chinese. The results indicate that the genetic testing before medication and the adjustment of escitalopram in the poor metabolizer should be considered in the clinical treatments in Chinese. The results provide the evidence of individual treatment of escitalopram in Chinese, which will be beneficial for the safer and more effective application of escitalopram in the Chinese population.Clinical Trial Registration: identifier ChiCTR1900027226.


1989 ◽  
Vol 8 (1) ◽  
pp. 39-43 ◽  
Author(s):  
De K. Sommers ◽  
J. Moncrieff ◽  
J. Avenant

1 The metabolic oxidation of metoprolol has been studied in a group of 98 San Bushmen. 2 The amounts of metoprolol and α-hydroxy metoprolol excreted in 0-8 h urine collection, after dosing with 100 mg metoprolol, were measured and the metabolic ratio (% dose excreted as metoprolol/% dose excreted as α-hydroxy metoprolol) calculated. 3 Frequency distribution and probit plots of the metabolic rate data showed a bimodal distribution with 4.1% of the population exhibiting slow metabolism with an MR > 10. 4 These results are much less than found in Caucasians (8.4%) but very different from the unimodal distribution found for Nigerians. 5 A previous study in the same group of Bushmen had revealed that 18 of 96 subjects were poor or non-metabolizers of debrisoquine to 4-hydroxy debrisoquine, but only one of the poor metoprolol metabolizers was a poor metabolizer of debrisoquine. 6 On the basis of these results, the claim of debrisoquine type of polymorphism for β-adrenoceptor antagonists found in Caucasians cannot be extrapolated to the San Bushmen, and one must query the use of debrisoquine as measure of oxidative status in any group other than Caucasians.


1995 ◽  
Vol 5 (4) ◽  
pp. 215-223 ◽  
Author(s):  
Vidar M. Steen ◽  
Ole A. Andreassen ◽  
Ann K. Daly ◽  
Toril Tefre ◽  
Anne-Lise Borresen ◽  
...  

1996 ◽  
Vol 6 (3) ◽  
pp. 269-272 ◽  
Author(s):  
Christoph Sachse ◽  
Jurgen Brockmoller ◽  
Steffen Bauer ◽  
Torsten Reum ◽  
Ivar Roots
Keyword(s):  
The Poor ◽  

2020 ◽  
Vol 127 (4) ◽  
pp. 354-357
Author(s):  
Maxim Kuzin ◽  
Isabel Scharrer ◽  
Daniele Nolan ◽  
Markus Baumgartner ◽  
Michael Paulzen ◽  
...  

1992 ◽  
Vol 5 (6) ◽  
pp. 317-336
Author(s):  
Y.W. Francis Lam ◽  
Milton V. Marshall

Many factors can influence the metabolism and disposition of drugs. Genetically determined differences in an individual's capacity to metabolize drugs are known causes of interindividual and interethnic variabilities in drug disposition and response. In general, a poor metabolizer for a specific metabolic pathway would likely develop adverse effects, and an extensive metabolizer for the same metabolic pathway might have less than optimal response. Although there are different types of polymorphism in drug metabolism, polymorphisms in debrisoquine-type oxidation, S-mephenytoin oxidation, and N-acetylation have been the most extensively studied. This article will present the basic concepts of pharmacogenetics, review the major types of metabolic polymorphisms, outline ways to determine phenotyping and genotyping differences in metabolizing enzyme activities, and discuss how these differences relate to drug metabolism, response, and toxicity. When evaluating drug response and adverse reactions in individual patients, an awareness of genetic differences in metabolic capacities would help contribute to optimization in drug therapy.


1991 ◽  
Vol 1 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Rachel Tyndale ◽  
Toshifumi Aoyama ◽  
Franck Broly ◽  
Tamihide Matsunaga ◽  
Tadanobu Inaba ◽  
...  

1999 ◽  
Vol 9 (3) ◽  
pp. 393-396 ◽  
Author(s):  
D. Marez-AIlorge ◽  
S. W. EHis ◽  
J-M. Lo Guidice ◽  
G. T. Tucker ◽  
E Broly

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