A prospective study to assess the association between genotype, phenotype and Prakriti in individuals on phenytoin monotherapy

• Main Authors: Saket J. Thaker, Prajakta P. Gandhe, Charuta J. Godbole, Shital R. Bendkhale, Nitin B. Mali, Urmila M. Thatte, Nithya J. Gogtay
• Format: Article
• Language: English
• Published: Elsevier 2017-01-01
• Series: Journal of Ayurveda and Integrative Medicine
• Subjects: Pharmacogenomics; Ayurveda; Epilepsy; Therapeutic drug monitoring; CYP2C9; CYP2C19
• Online Access: http://www.sciencedirect.com/science/article/pii/S0975947616303527

Background: Genetic polymorphisms in drug metabolizing enzymes (DMEs) impart distinct drug metabolizing capacity and a unique phenotype to an individual. Phenytoin has large inter-individual variability in metabolism due to polymorphisms in CYP2C9 and CYP2C19. As per Ayurveda, Prakriti imparts a unique phenotype to an individual. Objective: To assess whether Prakriti can substitute phenotyping [therapeutic drug monitoring (TDM)] and genotyping in individualizing therapy with phenytoin in epilepsy patients. Methods and materials: This was a cross-sectional study conducted over a period of three years. Prakriti was assessed using standardized and validated software. Polymorphisms in CYP2C9 and CYP2C19 were assessed using Polymerase Chain Reaction (PCR)-Restriction fragment length polymorphism (PCR-RFLP). Plasma concentrations of phenytoin (phenotype) were determined using reverse phase-high performance liquid chromatography (RF-HPLC). Results: Total 351 patients were enrolled for the study. Kapha vata (KV) (39%) was the predominantly observed Prakriti followed by vata kapha (VK) (20.8%) and vata pitta (VP) (8.83%) among the patients. The CYP2C9 and CYP2C19 genotype distributions were in accordance with Hardy–Weinberg equilibrium. There was no association between Prakriti and genotypes and Prakriti and phenotype (p > 0.05 each). Patients with CYP2C9 *1/*3 genotype were thrice more likely to have toxic plasma concentrations of phenytoin as compared to those with wild-type genotype (*1/*1) (Adjusted odds ratio – 3.36; 95% C.I. 1.61, 7.01). However, no such association was observed between polymorphisms of CYP2C19 and phenotype. Conclusions: We did not find any association between Prakriti and either phenotype or genotypes suggesting that Prakriti assessment would be of limited utility in individualizing phenytoin therapy in epilepsy patients.