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)," r="0.03;" p=".64)">
"Anti-inflammatory dose doxycycline (40 mg controlled-release) confers maximum anti-inflammatory efficacy in rosacea"
Theobald K, Bradshaw M, Leyden J
Skinmed. 2007 Sep-Oct ; 6(5): 221-6 (Hubmed.org)
Highlight :
Treatment Of Rosacea | Acne Rosacea Antibiotic
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)," r="0.03;" p=".64)">
"Anti-inflammatory dose doxycycline (40 mg controlled-release) confers maximum anti-inflammatory efficacy in rosacea"
Theobald K, Bradshaw M, Leyden J
Skinmed. 2007 Sep-Oct ; 6(5): 221-6 (Hubmed.org)
Highlight :
Treatment Of Rosacea | Acne Rosacea Antibiotic