| 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 | Klaus Theobald, Mark Bradshaw, James Leyden
(Affiliation: CollaGenex Pharmaceuticals Inc, 41 University Drive, Newtown, PA 18940, USA. ktheobald at collagenex.com)
|
| Journal | Skinmed
(Skinmed)
2007 Sep-Oct
Vol. 6
Issue 5
Pg. 221-6
ISSN: 1540-9740 United States |
| PMID | 17786099
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Anti-Inflammatory Agents
- Delayed-Action Preparations
- Doxycycline
|
| Topics |
- Anti-Inflammatory Agents
(administration & dosage, pharmacokinetics)
- Area Under Curve
- Clinical Trials, Phase I as Topic
- Delayed-Action Preparations
- Dose-Response Relationship, Drug
- Doxycycline
(administration & dosage, pharmacokinetics)
- Humans
- Linear Models
- Rosacea
(drug therapy)
|
