Ethnicity inter-ethnic difference

With respect to other ethnic groups, African Americans may have a differential sensitivity to weight gain on clozapine (de Leon etal, 2007). They may also require lower doses than Caucasians (Kelly et al, 2006) and inter-individual as well as ethnic responsiveness maybe partly explained by differences in dopamine receptor polymorphisms (Hwang et al, 2005). It is conceivable that side effects may also be differentially expressed based on pharmacodynamic differences resulting from polymorphisms in other receptor types (histaminergic, muscarinic, etc.). This area remains largely unexplored with respect to ethnic differences in antipsychotic side effects. 

Ethnic differences have been shown to influence response to psychotropic medications. Much of the focus on the explanation for such differences has been on drug-metabolizing (CYP) enzymes of the liver and their sway over pharmacokinetic factors. It is now well recognized that differences in the distribution of polymorphic variants of CYP enzymes exist between different ethnic groups. However, within ethnic groups there are considerable inter-individual variations in drug kinetics, which may not be accounted for solely by genetic variation. Responses to pharmacotherapy are multifaceted and involve the interaction of environmental and... 

Tab. 24.2 Inter-ethnic differences in the genotype and allele frequencies (%) of the MDR7 exon 26 C3435T polymorphism. The relevant reference is shown in parentheses...

Deficiency of thiopurine S-methyl transferase (TPMT) is another phenotype that exhibits inter-ethnic differences in frequency. TPMT is an enzyme that catalyzes methylation of therapeutic agents used in the treatment of acute lymphoblastic leukemia, rheumatoid arthritis, and autoimmune/inflammatory diseases, as well as in organ transplantation. Patients who have TPMT deficiency experience less efficient methylation and are at greater risk of fatal toxicity when treated with standard doses of fhiopurines. TPMT phenotype is defined by erythrocyte 6-mercapto-purine methylation. African American populations exhibit a 20% lower erythrocyte TPMT than Caucasian Americans, and persons of Chinese descent tend to exhibit greater activity than either of these other American subpopulations. 

Inter-ethnic differences in drug metabolism have become a trendy, and often quite exciting, line of enquiry. Results have often been quite surprising. For... 

These are a few illustrations of the emerging pattern of inter-ethnic differences in drug metabolism, which is genetically determined. 

Erratic DPD activity is a major cause of the marked pharmacokinetic variability of 5-FU. Drug-drug interactions (47,48), circadian patterns (12,49,50), and inter-gender (7,8) inter-ethnic differences (51,52,53,54,55) have been identified as putative causes for profound variations in DPD activities. Consequently, population studies of DPD activities displayed extremely wide ranges of values (17,56,57). 

Inoue, S. et al. Prediction of in vivo drug clearance from in vitro data. II potential inter-ethnic differences. Xenobiotica 2006, 36499-513. 

Inter-ethnicity differences observed with different CYP2C19 substrates for subjects with same genotype have been attributed to differences in substrate specificity or enzyme isoforms (Bertilsson 1992). The clearance of omeprazole is higher in Caucasian EMs than in Oriental EMs, due to an higher proportion of heterozygous EMs in this latter population (Ishizaki 1994). 

M. S., Cytochrome P450 3A genetic polymorphisms and inter-ethnic differences. Methods Find. Exp. Clin. Pharmacol. 27,559-567,2005 Sarlis,... 

There are wide inter-ethnic differences. When cases are discovered the family should be investigated for low plasma cholinesterase activity and affected individuals warned. 

Zhang Y, Bertilsson L, Lou T, et al., 1990. Diazepam metabolism in native Chinese, poor and extensive hydroxylators of S-mephenytoin inter-ethnic differences in comparison with White subjects . Clin. Pharmacol. Ther. 48 496—502. 

Yuan HY, Chen JJ, Lee MT, etal. A novel functional VKORCl promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. Hum Mol Genet 2005 14(13) 1745-5L... 

Many epidemiologic studies have identified inter-ethnic differences by substance of abuse within the U.S. [36], but local indigenous substance abuse trends in other geographic regions are difficult to identify because of basic socio-cultural differences in acceptable uses of psychoactive substances that preclude objective universal criteria for defining abuse. 

S-mephenytoin inter-ethnic differences in comparison with White subjects. Clin Pharmacol Therapeut 48 496-502. 

Hutson DH, Logan CJ (1986) The metabolic fate in rats of the pyrethroid insecticide WL85871,a mixture of two isomers of cypmnethrin. Pestic Sci 17 548-558 lARC (1991) Occupational exposures in insecticide application and some pesticides. lARC, Lyon Inoue S, Howgate EM, Rowland-Yeo K, Shimada T, Yamazaki H, Tucker GT, Rostami-Hodjegan A (2006) Prediction of in vivo drug clearance from in vitro data. D Potential inter-ethnic differences. Xenobiotica 36 499-513... 

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