squeegee
Banned
- Reaction score
- 132
sebazole (topical ketoconazole gel 2%) low systemic absorption for short treament periods
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.
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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.
Where can I find that???