PMID- 33009228
OWN - NLM
STAT- MEDLINE
DCOM- 20210726
LR  - 20221005
IS  - 1533-712X (Electronic)
IS  - 0271-0749 (Print)
IS  - 0271-0749 (Linking)
VI  - 40
IP  - 6
DP  - 2020 Nov/Dec
TI  - Randomized Controlled Crossover Trials of the Pharmacokinetics of PRC-063, a 
      Novel Multilayer Extended-Release Formulation of Methylphenidate, in Healthy 
      Adults.
PG  - 579-587
LID - 10.1097/JCP.0000000000001277 [doi]
AB  - 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.
FAU - Katzman, Martin A
AU  - Katzman MA
FAU - Mattingly, Greg
AU  - Mattingly G
FAU - Klassen, Larry J
AU  - Klassen LJ
AD  - Eden Mental Health Centre, Winkler, Manitoba, Canada.
FAU - Cataldo, Marc J
AU  - Cataldo MJ
AD  - Purdue Pharma L.P., Stamford, CT.
FAU - Donnelly, Graeme A E
AU  - Donnelly GAE
AD  - Purdue Pharma Canada, Pickering, Ontario, Canada.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - J Clin Psychopharmacol
JT  - Journal of clinical psychopharmacology
JID - 8109496
RN  - 0 (Capsules)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Delayed-Action Preparations)
RN  - 207ZZ9QZ49 (Methylphenidate)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Biological Availability
MH  - Capsules
MH  - Central Nervous System Stimulants/administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Cross-Over Studies
MH  - Delayed-Action Preparations
MH  - Drug Administration Schedule
MH  - Drug Compounding
MH  - Female
MH  - Gastrointestinal Absorption
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Methylphenidate/administration & dosage/adverse effects/*pharmacokinetics
MH  - Middle Aged
MH  - Quebec
MH  - Young Adult
PMC - PMC7643797
EDAT- 2020/10/04 06:00
MHDA- 2021/07/27 06:00
PMCR- 2020/11/05
CRDT- 2020/10/03 05:28
PHST- 2020/10/04 06:00 [pubmed]
PHST- 2021/07/27 06:00 [medline]
PHST- 2020/10/03 05:28 [entrez]
PHST- 2020/11/05 00:00 [pmc-release]
AID - 00004714-202011000-00010 [pii]
AID - JCP50947 [pii]
AID - 10.1097/JCP.0000000000001277 [doi]
PST - ppublish
SO  - J Clin Psychopharmacol. 2020 Nov/Dec;40(6):579-587. doi: 
      10.1097/JCP.0000000000001277.