Sonali_2013_CNS.Neurosci.Ther_19_91

BACKGROUND: Rivastigmine is an acetylcholinesterase inhibitor; the genotype data seen alongside the phenotype data explain the mutation or the molecular genetics involved and also help to relate the phenotype of an individual with their genotype. AIM: To determine the clinical effectiveness of CYP2D6, CYP3A4, CYP2C9/19, and UGT polymorphism on the steady-state plasma concentrations and therapeutic outcome of rivastigmine monotherapy and combination therapy in patients with Alzheimer's disease. RESULT: In this study, a significant allele frequency was observed for CYP2D6*3 polymorphism in patients under rivastigmine combination therapy (A>del = 0.50 [patients] and A>del = 0.20 [controls]), UGT2B7 (T = 0.17 [patients] and 0.33 [Controls], and UGT1A9*5 A = 0.58 [patients] and 0.26 [Controls]). The drug levels and P value of responders/nonresponders were found to be 0.17 +/- 0.08/0.22 +/- 0.16 and 0.574 for rivastigmine and 0.18 +/- 0.11/0.66 +/- 0.63 and 0.009 for rivastigmine in combination therapy and 1.40 +/- 0.65/0.59 +/- 0.84 and 0.05 for memantine in combination therapy. CONCLUSION: Poor metabolizer subjects of UGT2B7 polymorphism in patients under rivastigmine combination therapy have higher drug levels with a poor response to the drug treatments.