title: Safety and Pharmacokinetics of Once-Daily Dapsone Gel, 7.5% in Patients With Moderate Acne Vulgaris.
abstract: 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.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Jarratt
authors.forename: Terry M
authors.initials: TM
authors.lastname: Jones
authors.forename: Joan-En
authors.initials: JE
authors.lastname: Chang-Lin
authors.forename: Warren
authors.initials: W
authors.lastname: Tong
authors.forename: David R
authors.initials: DR
authors.lastname: Berk
authors.forename: Vince
authors.initials: V
authors.lastname: Lin
authors.forename: Alexandre
authors.initials: A
authors.lastname: Kaoukhov
mesh_terms: D000152:Acne Vulgaris / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D003622:Dapsone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004339:Drug Compounding; D004890:Erythema / Q000139:chemically induced; D005260:Female; D005782:Gels; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D005782:Gels; D003622:Dapsone