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| ORIGINAL ARTICLE
|Year : 2015 | Volume
| Issue : 2 | Page : 202--208
Critical appraisal of serum phenytoin variation with patient characteristics in a North Indian population
Sangeeta Sharma1, Fauzia Tabassum1, Pradeep Dwivedi2, Rachna Agarwal3, Suman Kushwaha4, Kiran Bala4, Sandeep Grover5, Ruchi Baghel5, Ritushree Kukreti6, Chandra B Tripathi7
1 Department of Neuropsychopharmacology, Institute of Human Behaviour and Allied Sciences, Dilshad Garden, Delhi, India
2 Department of Pharmacology and Therapeutics, King George's Medical University, Lucknow, Uttar Pradesh, India
3 Department of Neurochemistry, Institute of Human Behaviour and Allied Sciences, Dilshad Garden, Delhi, India
4 Department of Neurology, Institute of Human Behaviour and Allied Sciences, Dilshad Garden, Delhi, India
5 Senior Research Fellow, Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology, Delhi, India
6 Senior Scientist, Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology, Delhi, India
7 Department of Biostatistics, Institute of Human Behaviour and Allied Sciences, Dilshad Garden, Delhi, India
Context: Phenytoin (PHT) is one of the frontrunner drugs used as monotherapy in the management of epilepsy. It is also one of the most common drugs causing adverse drug reactions (ADRs). The aim of this study was to study the relationship between serum PHT levels and the age, gender, dosage and genetic polymorphisms in a North Indian population. This knowledge will help in devising drug dosage schedules in various sub-groups of patients as well as in reducing its ADRs.
Materials and Methods: A retrospective analysis of data of 6224 patients from 1998 to 2009 receiving PHT alone for greater than (>) 4 weeks was performed. Patients suspected of being non-compliant, being overdosed or having a hepatic or renal disorder were excluded from the study. Two thousand eight hundred and eighty-eight patients fulfilling the inclusion criteria were divided into three groups: children (1-18 years), adults (19-60 years) and elderly (>60 years).
Results: There was a male preponderance (80%) in all the groups. A significant difference was found in the mean dose between children and adults as well as between children and elderly (P = 0.00). Also, there was a significant difference in the mean concentration and dose ratio between children and adults (P = 0.00). However, a negative correlation was observed between the daily dose and dose ratio (r = -0.36, P = 0.00) that was highest (r = -0.58, P = 0.00) in the elderly. There was a significant gender difference in the mean dose in both children (P = 0.03) and adults (P = 0.00), whereas the mean concentration differed in adults only. Every fifth patient was an intermediate metabolizer (IM) (CYP2C9*1/*3) and showed higher steady state drug levels (>17 mg/L) compared with extensive metabolizers (EMs) (<12 mg/L). The genetic difference between IM and EM was more prevalent in the dose ratio at maintenance dose, with a mean ± SD of 4.041 ± 1.288 mg/L/mg/kg in nine patients carrying the CYP2C9*1/*3 genotype compared with 2.145 ± 0.817 mg/L/mg/kg in 26 patients carrying the CYP2C9*1/*1 genotype (P = 0.00).
Conclusion: North Indian female children and male adults frequently attain a higher serum concentration with the same dose when compared to the other groups. Absence of poor metabolizers may be responsible for a lower number of cases exhibiting toxicity in our population; however, this needs elucidation in a larger number of patients.
Dr. Sangeeta Sharma
Department of Neuropsychopharmacology, Institute of Human Behaviour and Allied Sciences, Delhi - 110 095
Source of Support: None, Conflict of Interest: None
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