CYP2C9 polymorphisms are associated with phenytoin toxicity in South-Indian epileptic patients
Background and Aims: The contribution of CYP2C9 in phenytoin metabolism is generally modest, but it increases with increasing serum phenytoin concentration. In the current study, we sought to study the association of CYP2C9*2 and CYP2C9*3 polymorphism with clinical and biochemical phenytoin toxicity...
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Published in | Journal of Dr. NTR university of health sciences Vol. 9; no. 2; pp. 92 - 97 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Wolters Kluwer India Pvt. Ltd
01.04.2020
Medknow Publications and Media Pvt. Ltd Wolters Kluwer Medknow Publications |
Subjects | |
Online Access | Get full text |
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Summary: | Background and Aims: The contribution of CYP2C9 in phenytoin metabolism is generally modest, but it increases with increasing serum phenytoin concentration. In the current study, we sought to study the association of CYP2C9*2 and CYP2C9*3 polymorphism with clinical and biochemical phenytoin toxicity in epileptic patients presenting to a tertiary care hospital in South-India.
Methods: In total, 50 patients on phenytoin therapy and clinically diagnosed with phenytoin toxicity in neurology outpatient department/casualty/intensive care unit and medicine wards were considered as cases. A total of 50 patients on phenytoin therapy without any evidence of toxicity were considered as controls. CYP2C9*2 (exon-3) and CYP2C9*3 (exon-7) gene polymorphisms were studied using the allele specific PCR method.
Results: Out of 100 patients, CYP2C9*2 polymorphism was seen in 8 (8%) patients in which 6 (12%) were cases and 2 (4%) were controls. CYP2C9*3 polymorphism was seen in 23 (23%) patients out of which 17 (34%) were cases and 6 (12%) were controls. Mean serum phenytoin level in cases was 24.23 ± 1.3 μg/ml, whereas in controls, it was 17.10 ± 0.6 μg/ml and the difference was statistically significant with P value <0.0001. Mean serum phenytoin level among patients with CYP2C9 polymorphism was 25.21 ± 4.72 μg/ml, whereas among patients without polymorphism, it was 17.51 ± 3.51 μg/ml (p < 0.0001).
Conclusion: Our findings conclude that the presence of CYP2C9*2 and CYP2C9*3 polymorphisms are associated with increased serum phenytoin levels and increased risk of clinical toxicity with phenytoin. |
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ISSN: | 2277-8632 2277-8632 |
DOI: | 10.4103/JDRNTRUHS.JDRNTRUHS_72_20 |