title: Transdermal Rivastigmine Delivery for Alzheimer Disease: Amenability of Exposure Predictions of Rivastigmine and Metabolite, NAP226-90, by Linear Regression Model Using Limited Samples.
abstract: OBJECTIVE
  Although an optimized delivery of rivastigmine for management of Alzhiemer disease (AD) is provided by the transdermal patch, it is critical to establish a limited sampling strategy for the measurement of exposure of rivastigmine/NAP226-90.
  
  
  METHODS
  The relationship Cmax versus AUC0-24h for rivastigmine/NAP226-90 was established by regression models. The derived regression equations enabled the prediction AUC0-24h for rivastigmine and NAP226-90. Models were evaluated using statistical criteria. Mixed model was used to predict AUC0-24h for rivastigmine/NAP226-90 from time points such as 8 (C8h), 12 (C12h), and 18 (C18h) hours.
  
  
  RESULTS
  Excellent correlation was established for between Cmax and AUC0-24h for rivastigmine and NAP226-90. AUC0-24h predictions of either rivastigmine or NAP226-90 were within 0.8- to 1.25-fold difference. The RMSE in the AUC0-24h predictions ranged from 17.6% to 21.9%, and the R for prediction were greater than 0.96 for both rivastigmine and NAP226-90. Use of mixed model for C8h, C12h, and C18h resulted in AUC0-24h within 1.5-fold difference for rivastigmine or NAP226-90.
  
  
  CONCLUSIONS
  Cmax of rivastigmine and NAP226-90 was highly correlated with the corresponding AUC0-24h values confirming the role of a time point closer to Cmax for an effective AUC measurement of rivastigmine or the metabolite.
authors.affiliation: Suramus Bio, Drug Development, Bangalore, Karnataka, India.
authors.forename: Nuggehally R
authors.initials: NR
authors.lastname: Srinivas
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D019540:Area Under Curve; D018592:Cross-Over Studies; D016208:Databases, Factual / Q000706:statistics & numerical data; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010627:Phenethylamines / Q000627:therapeutic use*; D010636:Phenols / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012016:Reference Values; D000068836:Rivastigmine / Q000008:administration & dosage* / Q000378:metabolism; D013997:Time Factors; D057968:Transdermal Patch
chemical_list: C494046:3-(1-dimethylaminoethyl)phenol; D018696:Neuroprotective Agents; D010627:Phenethylamines; D010636:Phenols; D000068836:Rivastigmine