PMID- 30810347
OWN - NLM
STAT- MEDLINE
DCOM- 20200629
LR  - 20200629
IS  - 1557-8992 (Electronic)
IS  - 1044-5463 (Print)
IS  - 1044-5463 (Linking)
VI  - 29
IP  - 3
DP  - 2019 Apr
TI  - Pharmacokinetics 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 Adults.
PG  - 181-191
LID - 10.1089/cap.2018.0122 [doi]
AB  - OBJECTIVES: 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  approximately 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.
FAU - Liu, Tao
AU  - Liu T
AD  - 1 Center for Translational Medicine, School of Pharmacy, University of Maryland, 
      Baltimore, Maryland.
FAU - Gobburu, Jogarao V S
AU  - Gobburu JVS
AD  - 1 Center for Translational Medicine, School of Pharmacy, University of Maryland, 
      Baltimore, Maryland.
FAU - Po, Michelle D
AU  - Po MD
AD  - 2 Highland Therapeutics Inc., Toronto, Ontario, Canada.
FAU - McLean, Angus
AU  - McLean A
AD  - 3 Ironshore Pharmaceuticals and Development, Inc., Camana Bay, Cayman Islands.
FAU - DeSousa, Norberto J
AU  - DeSousa NJ
AD  - 3 Ironshore Pharmaceuticals and Development, Inc., Camana Bay, Cayman Islands.
FAU - Sallee, Floyd R
AU  - Sallee FR
AD  - 3 Ironshore Pharmaceuticals and Development, Inc., Camana Bay, Cayman Islands.
FAU - Incledon, Bev
AU  - Incledon B
AD  - 3 Ironshore Pharmaceuticals and Development, Inc., Camana Bay, Cayman Islands.
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190227
PL  - United States
TA  - J Child Adolesc Psychopharmacol
JT  - Journal of child and adolescent psychopharmacology
JID - 9105358
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Delayed-Action Preparations)
RN  - 207ZZ9QZ49 (Methylphenidate)
SB  - IM
MH  - Adult
MH  - Attention Deficit Disorder with Hyperactivity/*drug therapy
MH  - Biological Availability
MH  - Central Nervous System Stimulants/*administration & dosage
MH  - Cross-Over Studies
MH  - Delayed-Action Preparations/*administration & dosage
MH  - Diet
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - *Methylphenidate/administration & dosage/pharmacokinetics
MH  - Middle Aged
MH  - Young Adult
PMC - PMC6479242
OTO - NOTNLM
OT  - attention-deficit/hyperactivity disorder
OT  - dose proportionality
OT  - food effect
OT  - methylphenidate
OT  - pharmacokinetics
OT  - relative bioavailability
EDAT- 2019/02/28 06:00
MHDA- 2020/07/01 06:00
PMCR- 2019/04/03
CRDT- 2019/02/28 06:00
PHST- 2019/02/28 06:00 [pubmed]
PHST- 2020/07/01 06:00 [medline]
PHST- 2019/02/28 06:00 [entrez]
PHST- 2019/04/03 00:00 [pmc-release]
AID - 10.1089/cap.2018.0122 [pii]
AID - 10.1089/cap.2018.0122 [doi]
PST - ppublish
SO  - J Child Adolesc Psychopharmacol. 2019 Apr;29(3):181-191. doi: 
      10.1089/cap.2018.0122. Epub 2019 Feb 27.