Sebazole (topical ketoconazole gel 2%) Low Systemic Absorption for Short Treatment Periods

Written by on March 20, 2006 in seborrheic dermatitis with 0 Comments

This study found that the topical use of Sebazole 2% Gel for short periods for seborrheic dermatitis did not result in significant systemic availability of the active ingredient Ketoconazole. That is it was hard to detect the ketoconazole in the blood after the gel was applied to the skin.

An open-label study to evaluate the systemic absorption of ketoconazole in subjects applying ketoconazole USP 2% topical gel for the treatment of seborrheic dermatitis, Vera Van de Velde, PhD, Princeton, NJ, United States; Charles Barranco, Brian Beger, Barrier Therapeutics, Princeton, NJ, United States

Methods: The systemic absorption of ketoconazole from ketoconazole USP 2% topical gel was evaluated in subjects with severe seborrheic dermatitis who applied the gel once daily for 2 weeks. Blood was sampled serially after 1 and 2 weeks of treatment, and ketoconazole plasma concentrations were determined by LC-MS/MS, with a LLOQ of 0.1 ng/mL. At Days 0, 7 and 15, clinical laboratory samples were collected and the percent body surface area affected (BSA) was estimated. Medication usage was assessed by weighing the tubes before and after dispensing. Adverse events were recorded.

Results: 18 subjects (10 male, 8 female) of various ethnicity completed the trial. Mean age was 45 years (19-70 years). Median total amount of gel applied was 4.6 g (range 1.65-46.3 g), equivalent to 91 mg (range 33-1389 mg) ketoconazole. The daily amount applied remained fairly constant. Mean BSA was 3.8% (1.0-14.0%) at baseline, 3.1% (0.3-14.0%) at Day 7 and 2.2% (0.0-14.0%) at Day 15. By Day 15, BSA declined . 50% in 14 subjects, 3 of whom had 0% BSA. In 1 subject ketoconazole plasma concentrations remained below the quantification limit throughout both sampling periods. In the others, quantifiable but very low plasma concentrations were seen at some or all sampling times. Median trough and peak plasma levels fluctuated between 0.22 and 0.52 ng/mL on Day 7 and between 0.21 and 0.52 ng/mL on Day 14. Median Tmax was 8 hours on Day 7 and 7 hours on Day 14. AUCt ranged between , 2.4 and 197 ng.h/mL and between , 2.4 and 117 ng.h/mL on Day 7 and 14, respectively. Clinical lab results were unremarkable. Only 1 adverse event, mild facial swelling, was reported. No deaths or serious adverse events occurred.

Conclusions: Subjects with severe seborrheic dermatitis who apply ketoconazole USP 2% topical gel once daily for 2 weeks to affected areas have limited systemic absorption of ketoconazole. These results agree with results from studies of other topical ketoconazole formulations where levels were non-quantifiable when less sensitive assays (LLOQ 1-5 ng/mL) were used. The median Cmax and AUC were 6700 and 1700 times lower than values reported after oral dosing of 200 mg ketoconazole. In the subject with the highest ketoconazole levels, Cmax and AUC were still 250 and 75 times lower than after 200 mg orally.

Author disclosure: Mr Barranco, Mr Beger and Dr Van de Velde are employees of Barrier Therapeutics. 100% sponsored by Barrier Therapeutics.

Sebazole is a topical formulation consisting of 2.0% ketoconazole, an antifungal agent, formulated in a waterless gel for once-daily application. The New Drug Application for Sebazole topical gel was submitted to the FDA in September 2005.

Poster Discussion Session P1901, American Academy of Dermatology, 64th Annual Meeting, March 3-7 2006, San Francisco.

Supplement to Journal of The American Academy of Dermatology, March 2006, Volume 54, Number 3.

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About the Author: David Pascoe started the Rosacea Support Group in October 1998. .

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