Open AccessClinical Effectiveness of Rivastigmine Monotherapy and Combination Therapy in Alzheimer's Patients
Author(s) -
Sonali Nirmal,
Tripathi Manjari,
Sagar Rajesh,
Velpandian Thirumurthy,
Subbiah Vivekanandhan
Publication year - 2013
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12036
Subject(s) - rivastigmine , combination therapy , medicine , pharmacology , memantine , galantamine , genotype , donepezil , acetylcholinesterase , pharmacogenetics , polymorphism (computer science) , oncology , gastroenterology , disease , dementia , biology , genetics , enzyme , gene , biochemistry
Summary 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 CYP 2D6, CYP 3A4, CYP 2C9/19, 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 CYP 2D6*3 polymorphism in patients under rivastigmine combination therapy ( A >del = 0.50 [patients] and A >del = 0.20 [controls]), UGT 2B7 (T = 0.17 [patients] and 0.33 [Controls], and UGT 1A9*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 UGT 2B7 polymorphism in patients under rivastigmine combination therapy have higher drug levels with a poor response to the drug treatments.