title: A hybrid Markov chain-von Mises density model for the drug-dosing interval and drug holiday distributions.
abstract: Lack of adherence is a frequent cause of hospitalizations, but its effects on dosing patterns have not been extensively investigated. The purpose of this work was to critically evaluate a novel pharmacometric model for deriving the relationships of adherence to dosing patterns and the dosing interval distribution. The hybrid, stochastic model combines a Markov chain process with the von Mises distribution. The model was challenged with electronic medication monitoring data from 207 hypertension patients and against 5-year persistence data. The model estimates distributions of dosing runs, drug holidays, and dosing intervals. Drug holidays, which can vary between individuals with the same adherence, were characterized by the patient cooperativity index parameter. The drug holiday and dosing run distributions deviate markedly from normality. The dosing interval distribution exhibits complex patterns of multimodality and can be long-tailed. Dosing patterns are an important but under recognized covariate for explaining within-individual variance in drug concentrations.
authors.affiliation: Department of Pharmaceutical Sciences and Neurology, State University of New York, 355 Kapoor Hall, Buffalo, New York, 14214-8033, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Fellows
authors.forename: Vivian
authors.initials: V
authors.lastname: Rodriguez-Cruz
authors.forename: Jenna
authors.initials: J
authors.lastname: Covelli
authors.forename: Alyssa
authors.initials: A
authors.lastname: Droopad
authors.forename: Sheril
authors.initials: S
authors.lastname: Alexander
authors.forename: Murali
authors.initials: M
authors.lastname: Ramanathan
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008390:Markov Chains; D055118:Medication Adherence; D015233:Models, Statistical; D013269:Stochastic Processes; D013997:Time Factors
chemical_list: D000959:Antihypertensive Agents