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dc.contributor.authorLiu, T.
dc.contributor.authorGobburu, J.V.S.
dc.contributor.authorPo, M.D.
dc.date.accessioned2019-09-13T16:42:01Z
dc.date.available2019-09-13T16:42:01Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85063951952&doi=10.1089%2fcap.2018.0122&partnerID=40&md5=f91fc9beaec7f89c45de55ddc9d06f7a
dc.identifier.urihttp://hdl.handle.net/10713/10716
dc.description.abstractObjectives: HLD200, an oral, once-daily, evening-dosed, delayed-release, and extended-release methylphenidate (DR/ER-MPH), was designed to provide efficacy from the early morning, throughout the day, and into the evening to individuals with attention-deficit/hyperactivity disorder. The objectives were to evaluate DR/ER-MPH pharmacokinetic (PK) properties in healthy adults, including dose proportionality, food effect, the potential of accumulation using multiple-dose modeling, and bioavailability compared to an immediate-release MPH (IR MPH). Methods: Three open-label, single-dose, crossover studies were conducted, all with a 7-day washout between treatments. In Study I, 20 subjects received evening-dosed DR/ER-MPH (20 and 100 mg) followed by a medium-fat breakfast; 13 subjects received a subsequent 100-mg dose of DR/ER-MPH followed by a low-fat breakfast. In Study II, 18 subjects were evaluated after receiving evening-dosed DR/ER-MPH (100 mg) under 3 conditions: immediately after a high-fat meal, sprinkled on applesauce, and in a fasted state. In Study III, 11 and 12 subjects received evening-dosed DR/ER-MPH (100 mg) and morning-dosed IR MPH (20 mg), respectively. Results: DR/ER-MPH demonstrated dose proportionality between 20-and 100-mg doses. DR/ER-MPH PK parameters were not significantly affected by breakfast content or by sprinkling capsule contents. A high-fat meal immediately preceding evening dosing did not affect total MPH exposure but lowered peak MPH exposure by 14% and 11% versus fasted and sprinkled states, and time to peak exposure was delayed by ?2.5 hours; these PK differences are unlikely to be clinically significant. Based on multiple-dose simulations using data from Study I, negligible accumulation of DR/ER-MPH was predicted. The relative bioavailability for DR/ER-MPH compared to IR MPH was 73.9%. No serious adverse events (AEs) were reported, and the observed AEs were consistent with MPH. There were no discontinuations in Studies I and III, but three participants withdrew in Study II due to AEs. Conclusions: Evening-dosed DR/ER-MPH demonstrated dose proportionality and can be administered with or without food. Significant accumulation is unlikely with multiple dosing. Copyright Tao Liu et al. 2019.en_US
dc.description.sponsorshipThey acknowledge the support of Ironshore Pharmaceuticals & Development, Inc. for funding.en_US
dc.description.urihttps://doi.org/10.1089/cap.2018.0122en_US
dc.language.isoen-USen_US
dc.publisherMary Ann Liebert Inc.en_US
dc.relation.ispartofJournal of Child and Adolescent Psychopharmacology
dc.subjectattention-deficit/hyperactivity disorderen_US
dc.subjectdose proportionalityen_US
dc.subjectfood effecten_US
dc.subjectmethylphenidateen_US
dc.subjectpharmacokineticsen_US
dc.subjectrelative bioavailabilityen_US
dc.titlePharmacokinetics of HLD200, a Delayed-Release and Extended-Release Methylphenidate: Evaluation of Dose Proportionality, Food Effect, Multiple-Dose Modeling, and Comparative Bioavailability with Immediate-Release Methylphenidate in Healthy Adultsen_US
dc.typeArticleen_US
dc.identifier.doi10.1089/cap.2018.0122
dc.identifier.pmid30810347


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