PMID- 31964449
OWN - NLM
STAT- MEDLINE
DCOM- 20211122
LR  - 20211122
IS  - 1092-8529 (Print)
IS  - 1092-8529 (Linking)
VI  - 25
IP  - 6
DP  - 2020 Dec
TI  - Single-dose pharmacokinetics of amphetamine extended-release tablets compared 
      with amphetamine extended-release oral suspension.
PG  - 774-781
LID - 10.1017/S1092852919001676 [doi]
AB  - OBJECTIVE: Evaluate the relative bioavailability of single-dose amphetamine 
      extended-release tablet (AMPH ER TAB) 20 mg, swallowed whole or chewed, and 
      amphetamine extended-release oral suspension (AMPH EROS) 2.5 mg/mL; evaluate food 
      effect on AMPH ER TAB. METHODS: Healthy volunteers (18-55 years) were randomized 
      to 1 dose of AMPH ER TAB 20 mg swallowed (fasted), chewed (fed/fasted), or 20 mg 
      AMPH EROS (fasted). A crossover study design was used. Plasma samples were 
      collected each period predose and at time points to 60 hours postdose. d- and 
      l-amphetamine were measured and pharmacokinetic (PK) was calculated (90% 
      confidence intervals of the ratios of the plasma levels) for AUC0-t, AUC0-infinity, and 
      Cmax. Comparative relative bioavailability between formulations was determined 
      when ratios were within 80% and 125%. Safety was also assessed. RESULTS: 
      Thirty-two subjects completed the study. AMPH ER TAB swallowed versus AMPH EROS 
      (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: 
      AUC0-t: 100.68% to 108.08%, AUC0-infinity: 101.47% to 109.52%, Cmax: 98.10% to 103.17%; 
      l: AUC0-t: 100.31% to 108.57%, AUC0-infinity: 101.27% to 111.09%, Cmax: 98.2% to 
      103.37%. For d- and l-amphetamine when the tablet is swallowed whole, Tmax was 
      5.00 hours (with a range of 2.00-9.00 hours). AMPH ER TAB chewed versus AMPH EROS 
      (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: 
      AUC0-t: 99.23% to 106.62%, AUC0-infinity: 99.58% to 107.59%, Cmax: 99.91% to 105.14%; l: 
      AUC0-t: 98.16% to 106.35%, AUC0-infinity: 98.44% to 108.11%, Cmax: 99.53% to 104.75%. 
      For d- and l-amphetamine when the tablet has been chewed, Tmax was 5.00 hours 
      (with a range of 3.00-7.00 hours). PK results were similar for patients in the 
      fasted and fed groups, indicative of no presence of food effect. No serious 
      adverse events (AEs) were reported, overall AE profiles between the tablet and 
      oral suspension were comparable without any unanticipated safety concerns. 
      CONCLUSIONS: Single doses of AMPH ER TAB for both d- and l-amphetamine 
      demonstrated comparable bioavailability to a 20 mg dose of AMPH EROS, 2.5 mg/mL 
      under fasted conditions when chewed and swallowed whole, and demonstrated 
      equivalent peak and overall exposure without apparent food effect. AMPH ER TAB 
      was well-tolerated and consistent with adverse events noted in other amphetamine 
      formulations.
FAU - Pardo, Antonio
AU  - Pardo A
AD  - Tris Pharma, Inc., Clinical and Medical Affairs. Monmouth Junction, New Jersey, 
      USA.
FAU - Kando, Judith C
AU  - Kando JC
AD  - Tris Pharma, Inc., Clinical and Medical Affairs. Monmouth Junction, New Jersey, 
      USA.
FAU - King, Thomas R
AU  - King TR
AUID- ORCID: 0000-0001-8487-6592
AD  - Tris Pharma, Inc., Clinical and Medical Affairs. Monmouth Junction, New Jersey, 
      USA.
FAU - Rafla, Eman
AU  - Rafla E
AD  - Tris Pharma, Inc., Clinical and Medical Affairs. Monmouth Junction, New Jersey, 
      USA.
FAU - Herman, Barry K
AU  - Herman BK
AD  - Tris Pharma, Inc., Clinical and Medical Affairs. Monmouth Junction, New Jersey, 
      USA.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20200122
PL  - United States
TA  - CNS Spectr
JT  - CNS spectrums
JID - 9702877
RN  - 0 (Dopamine Agents)
RN  - 0 (Tablets)
RN  - CK833KGX7E (Amphetamine)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Amphetamine/*administration & dosage/pharmacokinetics
MH  - Deglutition
MH  - Dopamine Agents/*administration & dosage/pharmacokinetics
MH  - *Drug Liberation
MH  - Female
MH  - Humans
MH  - Male
MH  - Mastication
MH  - Middle Aged
MH  - Tablets/administration & dosage
MH  - Tissue Distribution
OTO - NOTNLM
OT  - Pharmacokinetics
OT  - amphetamine
OT  - attention-deficit/hyperactivity disorder
OT  - formulations
OT  - stimulants
OT  - tablet
EDAT- 2020/01/23 06:00
MHDA- 2021/11/23 06:00
CRDT- 2020/01/23 06:00
PHST- 2020/01/23 06:00 [pubmed]
PHST- 2021/11/23 06:00 [medline]
PHST- 2020/01/23 06:00 [entrez]
AID - S1092852919001676 [pii]
AID - 10.1017/S1092852919001676 [doi]
PST - ppublish
SO  - CNS Spectr. 2020 Dec;25(6):774-781. doi: 10.1017/S1092852919001676. Epub 2020 Jan 
      22.