PMID- 29762909
OWN - NLM
STAT- MEDLINE
DCOM- 20200323
LR  - 20200323
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Print)
IS  - 2160-763X (Linking)
VI  - 8
IP  - 1
DP  - 2019 Jan
TI  - Open-Label, Dose-Escalation, Phase 1 Study of Safety and Single and Multiple-Dose 
      Pharmacokinetics of Dichlorphenamide in Healthy Volunteers.
PG  - 87-94
LID - 10.1002/cpdd.464 [doi]
AB  - Single-and multiple-dose pharmacokinetics and safety were investigated in this 
      phase 1 study of dichlorphenamide, a carbonic anhydrase inhibitor approved in the 
      United States for treatment of primary periodic paralysis. Dichlorphenamide was 
      administered to 6 cohorts (n = 6 each) of healthy adults. Cohorts A through E 
      received single doses of 25-400 mg followed by 50-800 mg/day in divided doses for 
      10 total doses. Cohort F (safety analysis only) received up to 28 titrated doses 
      from 100-800 mg/day. Plasma for pharmacokinetics sampling was obtained predose 
      and up to 48 hours postdose. Twenty-five of 36 enrolled subjects 
      completed. Median time to maximum plasma concentration ranged from 1.5-3 hours, 
      and mean half-life from 32-68 hours. Mean area under the concentration-time curve 
      from time 0 to tau (length of the dosing interval estimated using the trapezoidal 
      method) and maximum observed plasma concentration increased dose-proportionally 
      after multiple doses. The incidence and severity of adverse events (AEs) were 
      dose-related, with at least one mild AE reported among 17%, 17%, and 67% of 
      patients in cohorts A, B, and C, respectively; and at least one mild-to-moderate 
      AE among 100% of subjects in cohorts D, E, and F. One serious AE of rash was 
      reported in cohort F. Eleven subjects discontinued; 10 due to AEs at 400 or 800 
      mg/day (cohorts E and F), including 100% of cohort F. Hypokalemia contributed to 
      5 of 6 discontinuations in cohort F (all 800 mg/day).
CI  - (c) 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley 
      Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.
FAU - Cohen, Fredric
AU  - Cohen F
AD  - Strongbridge Biopharma, plc, Trevose, PA, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180515
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Carbonic Anhydrase Inhibitors)
RN  - VVJ6673MHY (Dichlorphenamide)
SB  - IM
MH  - Adult
MH  - Carbonic Anhydrase Inhibitors/*administration & dosage/adverse 
      effects/blood/pharmacokinetics
MH  - Dichlorphenamide/*administration & dosage/adverse effects/blood/pharmacokinetics
MH  - Drug Administration Schedule
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Single-Blind Method
PMC - PMC6585844
OTO - NOTNLM
OT  - Carbonic anhydrase
OT  - dichlorphenamide
OT  - periodic paralysis
OT  - pharmacokinetics
OT  - sulfonamide
EDAT- 2018/05/16 06:00
MHDA- 2020/03/24 06:00
PMCR- 2019/06/20
CRDT- 2018/05/16 06:00
PHST- 2017/10/06 00:00 [received]
PHST- 2018/02/27 00:00 [accepted]
PHST- 2018/05/16 06:00 [pubmed]
PHST- 2020/03/24 06:00 [medline]
PHST- 2018/05/16 06:00 [entrez]
PHST- 2019/06/20 00:00 [pmc-release]
AID - CPDD464 [pii]
AID - 10.1002/cpdd.464 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2019 Jan;8(1):87-94. doi: 10.1002/cpdd.464. Epub 2018 
      May 15.