Clindagel (Clindamycin Phosphate Topical Gel) - Description and Clinical Pharmacology

DESCRIPTION

Clindagel^® (clindamycin phosphate gel) topical gel, 1%, a topical antibiotic, contains clindamycin phosphate, USP, at a concentration equivalent to 10 mg clindamycin per gram in a gel vehicle consisting of carbomer 941, methylparaben, polyethylene glycol 400, propylene glycol, sodium hydroxide, and purified water. Chemically, clindamycin phosphate is a water-soluble ester of the semi-synthetic antibiotic produced by a 7 (S)-chloro-substitution of the 7 (R)-hydroxyl group of the parent antibiotic, lincomycin, and has the structural formula represented below:

The chemical name for clindamycin phosphate is methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl- trans -4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L- threo -(alpha)-D- galacto -octopyranoside 2-(dihydrogen phosphate).

CLINICAL PHARMACOLOGY

Pharmacokinetics:    In an open label, parallel group study of 24 patients with acne vulgaris, once-daily topical administration of approximately 3-12 grams/day of Clindagel^® for five days resulted in peak plasma clindamycin concentrations that were less than 5.5 ng/mL.

Following multiple applications of Clindagel^® less than 0.04% of the total dose was excreted in the urine.

Microbiology:    Although clindamycin phosphate is inactive in vitro, rapid in vitro hydrolysis converts this compound to clindamycin which has antibacterial activity. Clindamycin inhibits bacteria protein synthesis at the ribosomal level by binding to the 50S ribosomal subunit and affecting the process of peptide chain initiation. In vitro studies indicated that clindamycin inhibited all tested Propionibacterium acnes cultures at a minimum inhibitory concentration (MIC) of 0.4 µg/mL. Cross-resistance has been demonstrated between clindamycin and erythromycin.

CLINICAL STUDIES

In one 12-week multicenter, randomized, evaluator-blind, vehicle-controlled, parallel comparison clinical trial in which patients used Clindagel^® (clindamycin phosphate topical gel, 1%) once daily or the vehicle gel once daily, in the treatment of acne vulgaris of mild to moderate severity, Clindagel^® applied once daily was more effective than the vehicle applied once daily. The mean percent reductions in lesion counts at the end of treatment in this study are shown in the following table:

There was a trend in the investigator's global assessment of the results which favored Clindagel^® QD over the vehicle QD.

In a contact sensitization study, four of the 200 subjects appeared to develop suggestive evidence of allergic contact sensitization to Clindagel^® . There was no signal for contact sensitization in the clinical trials under normal use conditions.