DESCRIPTION
DIFFERIN® (adapalene) Cream, 0.1%, contains adapalene 0.1% in an aqueous cream emulsion consisting of carbomer 934P, cyclomethicone, edetate disodium, glycerin, methyl glucose sesquistearate, methylparaben, PEG-20 methyl glucose sesquistearate, phenoxyethanol, propylparaben, purified water, squalane, and trolamine.
The chemical name of adapalene is 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid. It is a white to off-white powder which is soluble in tetrahydrofuran, sparingly soluble in ethanol, and practically insoluble in water. The molecular formula is C28H28O3 and molecular weight is 412.53. Adapalene is represented by the following structural formula.
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CLINICAL PHARMACOLOGY
Mechanism of Action
Adapalene acts on retinoid receptors. Biochemical and pharmacological profile studies have demonstrated that adapalene is a modulator of cellular differentiation, keratinization, and inflammatory processes all of which represent important features in the pathology of acne vulgaris.
Mechanistically, adapalene binds to specific retinoic acid nuclear receptors but does not bind to the cytosolic receptor protein. Although the exact mode of action of adapalene is unknown, it is suggested that topical adapalene normalizes the differentiation of follicular epithelial cells resulting in decreased microcomedone formation.
Pharmacokinetics
Absorption of adapalene from DIFFERIN® Cream through human skin is low. In a pharmacokinetic study with six acne patients treated once daily for 5 days with 2 grams of DIFFERIN® Cream applied to 1000 cm2 of acne involved skin, there were no quantifiable amounts (limit of quantification = 0.35 ng/mL) of adapalene in the plasma samples from any patient. Excretion appears to be primarily by the biliary route.
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CLINICAL STUDIES
Two vehicle-controlled clinical studies were conducted in patients 12 to 30 years of age with mild to moderate acne vulgaris, in which DIFFERIN® Cream was compared with its vehicle. Patients were instructed to apply their treatment medication once daily at bedtime for 12 weeks. In one study patients were provided with a soapless cleanser and were encouraged to refrain from using moisturizers. No other topical medications, other than DIFFERIN® Cream, were to be applied to the face during the studies. DIFFERIN® Cream was significantly more effective than its vehicle in the reduction of acne lesion counts. The mean percent reduction in lesion counts from baseline after treatment for 12 weeks are presented in the following table:
MEAN PERCENT REDUCTION IN LESION COUNTS FROM BASELINE TO WEEK 12
Efficacy Variable
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Study No. 1
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Study No. 2
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Adapalene Cream, 0.1%
N=119
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Cream Vehicle
N=118
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Adapalene
Cream, 0.1%
N=175
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Cream
Vehicle
N=175
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Non-inflammatory lesions |
34%
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18% |
35% |
15% |
Inflammatory lesions |
32% |
17% |
14% |
6% |
Total lesions |
34% |
18% |
30%
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15% |
The trend in the Investigator’s global assessment of severity supported the efficacy of DIFFERIN® Cream when compared to the cream vehicle.
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