title: A prospective study to assess the association between genotype, phenotype and Prakriti in individuals on phenytoin monotherapy.
abstract: 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
  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.
authors.affiliation: Dept. of Clinical Pharmacology, 1st Floor New M.S. Building, Seth G.S. Medical College & K.E.M.H., Parel, Mumbai, 400012, India.
authors.forename: Saket J
authors.initials: SJ
authors.lastname: Thaker
authors.affiliation: Dept. of Clinical Pharmacology, 1st Floor New M.S. Building, Seth G.S. Medical College & K.E.M.H., Parel, Mumbai, 400012, India.
authors.forename: Prajakta P
authors.initials: PP
authors.lastname: Gandhe
authors.affiliation: Dept. of Clinical Pharmacology, 1st Floor New M.S. Building, Seth G.S. Medical College & K.E.M.H., Parel, Mumbai, 400012, India.
authors.forename: Charuta J
authors.initials: CJ
authors.lastname: Godbole
authors.affiliation: Dept. of Clinical Pharmacology, 1st Floor New M.S. Building, Seth G.S. Medical College & K.E.M.H., Parel, Mumbai, 400012, India.
authors.forename: Shital R
authors.initials: SR
authors.lastname: Bendkhale
authors.affiliation: Dept. of Clinical Pharmacology, 1st Floor New M.S. Building, Seth G.S. Medical College & K.E.M.H., Parel, Mumbai, 400012, India.
authors.forename: Nitin B
authors.initials: NB
authors.lastname: Mali
authors.affiliation: Dept. of Clinical Pharmacology, 1st Floor New M.S. Building, Seth G.S. Medical College & K.E.M.H., Parel, Mumbai, 400012, India. Electronic address: urmilathatte@kem.edu.
authors.forename: Urmila M
authors.initials: UM
authors.lastname: Thatte
authors.affiliation: Dept. of Clinical Pharmacology, 1st Floor New M.S. Building, Seth G.S. Medical College & K.E.M.H., Parel, Mumbai, 400012, India.
authors.forename: Nithya J
authors.initials: NJ
authors.lastname: Gogtay
keywords: Ayurveda; CYP2C19; CYP2C9; Epilepsy; Pharmacogenomics; Therapeutic drug monitoring