Randomized Controlled Crossover Trials of the Pharmacokinetics of PRC-063, a Novel Multilayer Extended-Release Formulation of Methylphenidate, in Healthy Adults
| Autor: | Greg Mattingly, Larry J. Klassen, Graeme A.E. Donnelly, Marc Cataldo, Martin A Katzman |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male animal structures Evening FOQUEST Adolescent Drug Compounding Original Contributions Cmax Administration Oral Biological Availability Capsules methylphenidate Pharmacology Drug Administration Schedule 03 medical and health sciences Young Adult 0302 clinical medicine Pharmacokinetics Medicine Humans ADHD Pharmacology (medical) Dosing Cross-Over Studies business.industry Methylphenidate Area under the curve Quebec Middle Aged Crossover study Adhansia Healthy Volunteers 030227 psychiatry Psychiatry and Mental health Gastrointestinal Absorption Delayed-Action Preparations ComputingMethodologies_DOCUMENTANDTEXTPROCESSING Methylphenidate Hydrochloride Central Nervous System Stimulants Female business pharmacokinetics 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Clinical Psychopharmacology |
| ISSN: | 1533-712X |
| Popis: | Supplemental digital content is available in the text. Purpose/Background PRC-063 is a once-daily, extended-release oral formulation of methylphenidate hydrochloride developed to provide early and prolonged symptom improvement in patients with attention-deficit/hyperactivity disorder. Methods/Procedures We conducted 3 randomized, open-label crossover studies of the pharmacokinetics of PRC-063 in healthy, nonobese men and women aged 18 to 45 years. PRC-063 (100 mg/d) was compared with immediate-release methylphenidate (20 mg, 3 times daily) when administered on a single day under fasted and fed conditions and at steady state (day 5 of repeat dosing under fasted conditions). The pharmacokinetics of PRC-063 administered as capsule contents sprinkled on apple sauce, yoghurt, or ice cream were also investigated. Findings/Results PRC-063 demonstrated biphasic absorption, with 2 distinct peak plasma concentrations. Intake of a high-fat, high-calorie meal did not increase the peak plasma methylphenidate concentration (Cmax) or extent of absorption (area under the curve), however; it resulted in slower uptake versus a fasted state. During repeated dosing, steady state was reached with no further accumulation of methylphenidate from day 3. At steady state, PRC-063 gave higher evening and trough plasma methylphenidate levels than immediate-release methylphenidate (3 times daily). The pharmacokinetics of PRC-063 sprinkled on food were comparable to that of intact capsules. Reported adverse events (AEs) were consistent with the established safety profile of methylphenidate. There were no serious AEs, but 3 subjects discontinued the repeat-dosing study because of AEs assessed as possibly related to study treatment. Implications/Conclusions Our data indicate that PRC-063 can be taken with or without food or by sprinkling capsule contents on food. |
| Databáze: | OpenAIRE |
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