caa a22 4500 605533865 CHVBK 20210128100840.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s10928-015-9414-4 doi (NATIONALLICENCE)springer-10.1007/s10928-015-9414-4 Development and application of an aggregate adherence metric derived from population pharmacokinetics to inform clinical trial enrichment [Elektronische Daten] [Jonathan Knights, Shashank Rohatagi] Nonadherence to prescribed medication is a common barrier to effective treatment, and current options to determine adherence are limited. This study describes development of an aggregate adherence measure based on population pharmacokinetics (PK), and its comparison to a subjective questionnaire, the Morisky 8-item medication adherence scale (MMAS8), in a trial of psychiatric patients on stable doses of oral aripiprazole. A comprehensive model was first built using plasma drug concentration data from 24 clinical studies comprising 448 patients with over 13,500 observations. Application of this model to independent patient profiles for a given drug-dosing regimen were used to generate the primary aggregate adherence metric, a ratio of observed versus expected plasma exposures at steady-state. Although the metric is capable of comparing relative adherence across groups, simulations showed that the metric is not sufficiently sensitive as an individual diagnostic in all cases. There were no trends observed between results from calculated aggregate adherence metrics and total scores from MMAS8 in a single-visit clinical trial of 47 patients with bipolar 1 disorder or schizophrenia who were on stable doses of aripiprazole, although a strong association was observed for one MMAS8 question. The range of the metric calculated for patients was between 0.16 and 3.15. The described approach of a novel "reverse” application of population PK to quantify relative adherence with an aggregate measure may be influential for both clinical and pharmacometric communities. The Author(s), 2015 Aggregate adherence metric nationallicence Population pharmacokinetics nationallicence Steady-state plasma drug concentrations nationallicence Simulation nationallicence Aripiprazole nationallicence Knights Jonathan Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center Blvd. Suite 300, 08540, Princeton, NJ, USA aut Rohatagi Shashank Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center Blvd. Suite 300, 08540, Princeton, NJ, USA aut Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/3(2015-06-01), 263-273 1567-567X 42:3<263 2015 42 10928 https://doi.org/10.1007/s10928-015-9414-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10928-015-9414-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Knights Jonathan Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center Blvd. Suite 300, 08540, Princeton, NJ, USA aut NATIONALLICENCE 700 1- Rohatagi Shashank Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center Blvd. Suite 300, 08540, Princeton, NJ, USA aut NATIONALLICENCE 773 0- Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/3(2015-06-01), 263-273 1567-567X 42:3<263 2015 42 10928