title: Anti-inflammatory dose doxycycline (40 mg controlled-release) confers maximum anti-inflammatory efficacy in rosacea.
abstract: BACKGROUND
  Two large clinical trials have recently demonstrated the efficacy of a 40-mg controlled-release formulation of doxycycline in the treatment of rosacea, a dose well below the conventional level of 100 to 200 mg/d. Since no formal dose-response studies have been conducted, the authors analyzed phase 3 data to determine whether a dose-efficacy relationship exists.
  
  
  METHODS
  Standard parametric regression analyses were used to estimate the correlations between dose (mg/kg body weight) and overall drug exposure (area under the curve [AUC]) in a phase 1 pharmacokinetic study and between dose and efficacy (mean change from baseline in total inflammatory lesion count at week 16) in 2 pooled phase 3 clinical efficacy studies. Additional regressions were run at each visit for the clinical efficacy studies to determine whether results differed across visits. A regression analysis was also performed in a subset of patients who showed a greater efficacy response.
  
  
  RESULTS
  We found overall drug exposure (AUC) to have a highly significant correlation with dose (mg/kg) (r=0.49; P=.006). In contrast, clinical efficacy did not correlate with dose at any of the visits at week 3 (r=0.01; P=.85), week 6 (r=0.04; P=.53), week 12 (r<0.01; P=.98), and week 16 (r=0.03; P=.64) or among the subset of patients who showed greater clinical benefit.
  
  
  CONCLUSIONS
  Higher mg/kg doses led to higher plasma concentrations but did not lead to increased clinical efficacy. Anti-inflammatory dose doxycycline (40-mg controlled-release formulation) conferred peak anti-inflammatory efficacy in the treatment of rosacea.
authors.affiliation: CollaGenex Pharmaceuticals Inc, 41 University Drive, Newtown, PA 18940, USA. ktheobald@collagenex.com
authors.forename: Klaus
authors.initials: K
authors.lastname: Theobald
authors.forename: Mark
authors.initials: M
authors.lastname: Bradshaw
authors.forename: James
authors.initials: J
authors.lastname: Leyden
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D017321:Clinical Trials, Phase I as Topic; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D016014:Linear Models; D012393:Rosacea / Q000188:drug therapy*