PMID- 27741344
OWN - NLM
STAT- MEDLINE
DCOM- 20170426
LR  - 20170426
IS  - 1545-9616 (Print)
IS  - 1545-9616 (Linking)
VI  - 15
IP  - 10
DP  - 2016 Oct 1
TI  - Safety and Pharmacokinetics of Once-Daily Dapsone Gel, 7.5% in Patients With 
      Moderate Acne Vulgaris.
PG  - 1250-1259
AB  - BACKGROUND: Reducing the dosing frequency of topical acne treatments to once 
      daily may improve adherence. OBJECTIVE: Evaluate pharmacokinetics (PK), safety, 
      and tolerability of 3 formulations of once-daily dapsone gel, 7.5% and of 
      twice-daily dapsone gel, 5% over 28 days in patients with moderate acne vulgaris. 
      METHODS: This phase 1, multicenter, parallel-group study randomized males and 
      females aged 16 to 35 years to 1 of 3 dapsone gel, 7.5% formulations (DAP-11078, 
      DAP-11079, or DAP-11080 double-blind; applied once daily) or to dapsone gel, 5% 
      (investigator-blinded only, applied twice-daily). Blood samples were collected 
      for PK assessments of dapsone and its metabolites, N-acetyl dapsone (NAD) and 
      dapsone hydroxylamine (DHA), before the morning dose on days 1, 7, 14, 18, 21, 
      26, 27, and 28, and at several follow-up time points (days 29-32). Safety profile 
      assessments included adverse events (AEs), physical examinations, laboratory 
      tests, and local tolerability assessments. RESULTS: Steady-state dapsone, NAD, 
      and DHA concentrations were reached within 7 days of the first dose in all 
      treatment groups. Daily systemic exposures of the 3 dapsone gel, 7.5% 
      formulations were approximately 25% to 40% lower than that for dapsone gel, 5%, 
      and these differences were statistically significant. Among the 3 dapsone gel, 
      7.5% formulations, the highest daily exposure of dapsone (per the AUC) was 
      observed with DAP-11080, with respective Cmax and AUC0-24 being approximately 
      28.6% and 28.7% lower relative to dapsone gel, 5%. Most AEs were mild to moderate 
      in intensity. The safety profiles for all 3 formulations of once-daily dapsone, 
      7.5% gel and twice-daily dapsone gel, 5% were similar following 28 days of 
      topical administration. All 4 dapsone formulations were well tolerated. 
      CONCLUSIONS: This study demonstrated lower systemic exposure with all 3 
      once-daily dapsone gel, 7.5% formulations than with twice-daily dapsone gel, 5%. 
      All 4 formulations were well tolerated and demonstrated similar safety profiles. 
      <br /><br /> <em>J Drugs Dermatol.</em> 2016;15(10):1250-1259.
FAU - Jarratt, Michael T
AU  - Jarratt MT
FAU - Jones, Terry M
AU  - Jones TM
FAU - Chang-Lin, Joan-En
AU  - Chang-Lin JE
FAU - Tong, Warren
AU  - Tong W
FAU - Berk, David R
AU  - Berk DR
FAU - Lin, Vince
AU  - Lin V
FAU - Kaoukhov, Alexandre
AU  - Kaoukhov A
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - United States
TA  - J Drugs Dermatol
JT  - Journal of drugs in dermatology : JDD
JID - 101160020
RN  - 0 (Anti-Infective Agents)
RN  - 0 (Gels)
RN  - 8W5C518302 (Dapsone)
SB  - IM
MH  - Acne Vulgaris/diagnosis/*drug therapy/*metabolism
MH  - Administration, Topical
MH  - Adolescent
MH  - Adult
MH  - Anti-Infective Agents/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Dapsone/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Drug Compounding
MH  - Erythema/chemically induced
MH  - Female
MH  - Gels
MH  - Humans
MH  - Male
MH  - Young Adult
EDAT- 2016/10/16 06:00
MHDA- 2017/04/27 06:00
CRDT- 2016/10/15 06:00
PHST- 2016/10/15 06:00 [entrez]
PHST- 2016/10/16 06:00 [pubmed]
PHST- 2017/04/27 06:00 [medline]
AID - S1545961616P1250X [pii]
PST - ppublish
SO  - J Drugs Dermatol. 2016 Oct 1;15(10):1250-1259.