Frequency of impaired mephenytoin 4′‐hydroxylation in an Indian population [letter]

Bs, Doshi; Rd, Kulkarni; Bl, Chauhan; Wilkinson, G. R.

doi:10.1111/j.1365-2125.1990.tb03850.x

Cited by 11 publications

(4 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data for both debrisoquine and mephenytoin oxidation are similar to those obtained in Indians living in Bombay, which is in the North-West part of the country [7,8]. It is well-established that the Sinhalese are immigrants from the Indian mainland but there is disagreement as to whether they came originally from the North-East or the North-West part of the country [16].…”

Section: Discussionsupporting

confidence: 82%

“…However, the results of blood genetic marker analysis have not revealed any differences between Sinhalese and Tamils [16]. The findings of Idle & Smith [7] and Doshi et al [8] in Northern Indians are similar to the present findings in Sinhalese and indicate similarity to Orientals rather than to white Caucasians with respect to the prevalence of the poor metaboliser phenotypes. This is at variance with data from DNA marker studies, the results of which indicate that Indian and European populations have a common Caucasoid ancestor genetically distinct from those of Oriental populations [17].…”

Section: Discussionsupporting

confidence: 80%

“…Although the peoples of the Indian sub-continent account for a substantial proportion (about 20%) of the world's population, the only ethnic group in this region to be studied with respect to polymorphic drug oxidation is that of Indians resident in Bombay, of which 1-3% [7] and 21% [8] were found to be poor metabolisers of debrisoquine and mephenytoin, respectively. We now report data on the pattern of metabolism of these two drugs in a Sinhalese population resident in and around Colombo, Sri Lanka.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Debrisoquine and mephenytoin oxidation in Sinhalese: a population study.

Weerasuriya

Jayakody

Smith

et al. 1994

Brit J Clinical Pharma

View full text Add to dashboard Cite

The frequency distributions of the 0-8 h urinary metabolic ratios of debrisoquine and mephenytoin were measured in 111 healthy, unrelated Sinhalese resident in Sri Lanka. Blood samples were taken from 77 of these subjects for CYP2D6 genotyping.Bimodality in the distribution of the logio debrisoquine/4-hydroxydebrisoquine ratio was not evident from visual inspection and by kernel density analysis. The results of genotyping indicated that 82% of the population were either homozygous for the wild-type CYP2D6 gene or heterozygous for the wild type allele and the whole gene deletion. Eighteen per cent of the Sinhalese population were heterozygous for the CYP2D6B mutation and the wild-type allele. All of these genotypes give rise to the extensive metaboliser phenotype in white Caucasians. No CYP2D6A mutations were identified and no individuals who were homozygous for the mutant alleles were detected, which is in accord with an absence of phenotypic poor metabolisers of debrisoquine. The mutant CYP2D6 allele frequency in Sinhalese (9%) is only half that observed in white Caucasians. The S/R-mephenytoin ratio ranged from 0.09 to 2.27 (median 0.38). By visual inspection and kernel density analysis the distribution of the S/R-mephenytoin ratio was bimodal and, using a value of 0.9 for the antimode, 16 (14%) subjects were poor metabolisers. In conclusion, the prevalence of the poor metaboliser phenotype in Sinhalese appears much lower for debrisoquine and higher for mephenytoin than in white Caucasians. These findings are similar to those observed in Indians living in Bombay and in Oriental populations.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Debrisoquine and mephenytoin oxidation in Sinhalese: a population study.

Weerasuriya

Jayakody

Smith

et al. 1994

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…[ 14 ] A phenotypic study carried out in people living in Bombay, which is the North West part of India shows low prevalence (3%) of the PM phenotype. [ 15 16 ] The Sri Lankan Tamils are the descendants of Tamils from South India who came to the Island and settled down at various times in the past when Sri Lanka was invaded by South Indian rulers. The Moors are the descendants of Arab traders.…”

Section: Discussionmentioning

confidence: 99%

Genetic variants in the cytochrome P450 2D6 gene in the Sri Lankan population

et al. 2013

View full text Add to dashboard Cite

INTRODUCTION:Cytochrome P450 2D6 (CYP2D6) enzymes are involved in the metabolism of a large number of commonly prescribed drugs such as antidepressants and cardiovascular drugs. The CYP2D6 *3, *4 and *14 variants associated with the loss of enzyme function; CYP2D6 *10 and *17 variants with reduced enzyme function; and CYP2D6 *2 variant with no effect on enzyme function. Establishing the frequency of these variant alleles in Sri Lankan population would be useful for optimizing pharmacotherapy with CYP2D6-substrate drugs.OBJECTIVE:The objective of this study was to determine the prevalence of CYP2D6 *2, *3, *4, *10, *14 and *17 variants in the main ethnic groups in the Sri Lankan population.MATERIALS AND METHODS:A total of 90 deoxyribonucleic acid (DNA) samples (30 each from Sinhalese, Tamils and Moors) were selected from a DNA resource at the Human Genetic Unit, Faculty of Medicine, University of Colombo. This collection had been made for population genetic studies from a random population based volunteers. Genotyping was performed using published polymerase chain reaction/restriction fragment length polymorphism methods.RESULTS:The prevalence of the CYP2D6 variants in Sinhalese, Sri Lankan Tamils and Moors respectively were CYP2D6 *2: 37%, 41.6% and 37.9%; CYP2D6 *3: 60.3%, 45% and 30%; CYP2D6 *4: 21.6%, 6.6% and 8.3%; CYP2D6 *10: 40%, 35% and 44%. CYP2D6 *14 and *17 variants were not identified.CONCLUSION:CYP2D6*3, *4 and *10 variants, which are associated with reduced or loss of CYP2D6 enzyme function were found in our population in significant frequencies. CYP2D6*4, which is reported to be a Caucasian variant was also found in all three ethnic groups.

show abstract

Psychiatry, psychopharmacology and P-450s

Glue¹,

Banfield²

1996

Hum. Psychopharmacol. Clin. Exp.

View full text Add to dashboard Cite

The cytochrome P-450 enzyme family is one of the major drug metabolizing systems in man. Over the last decade, advances in molecular biology, in vitro and clinical pharmacology techniques have increased our understanding of their role in the metabolism of psychotropic drugs, the effects of psychotropics on enzyme inhibition and induction, and how the pharmacokinetics of psychotropics are affected by changes in enzyme activity. There is also greater awareness of the influence of factors such as age, gender, race and environment on enzyme activity. This information can be of considerabIe assistance to psychiatrists, to help with rational prescribing, or to prevent or minimize the potential for drug interactions.

show abstract

Frequency of impaired mephenytoin 4′‐hydroxylation in an Indian population [letter]

Cited by 11 publications

References 10 publications

Debrisoquine and mephenytoin oxidation in Sinhalese: a population study.

Debrisoquine and mephenytoin oxidation in Sinhalese: a population study.

Genetic variants in the cytochrome P450 2D6 gene in the Sri Lankan population

Psychiatry, psychopharmacology and P-450s

Contact Info

Product

Resources

About