1. Human urinary excretion kinetics of the antimycotic climbazole: Biomonitoring of two new metabolites after oral and dermal dosage.
- Author
-
Schönrath I, Schmidtkunz C, Ebert KE, Küpper K, Brüning T, Koch HM, and Leng G
- Subjects
- Humans, Administration, Oral, Adult, Male, Female, Biological Monitoring methods, Young Adult, Hair Preparations, Middle Aged, Skin Absorption, Imidazoles, Administration, Cutaneous, Antifungal Agents urine, Antifungal Agents pharmacokinetics, Antifungal Agents administration & dosage
- Abstract
Climbazole is an antimycotic compound used in cosmetic products as a preservative or as an active ingredient in anti-dandruff (AD) formulations. In this study we provide human toxicokinetic data on climbazole. Using our previously published analytical method, we investigated the urinary excretion of two climbazole metabolites, (OH)
2 -climbazole and cx-OH-climbazole, for 48 h after oral ingestion (n = 5, 49-77 µg/kg bw) and for 72 h after dermal application of either a climbazole-containing rinse-off AD shampoo or a leave-on hair tonic (n = 2×3). In total, 23.9 % (18.0-33.4 %) of the oral dose were excreted as the two abovementioned metabolites over 48 h. In one volunteer, who used an over-the-counter phytopharmaceutical, metabolite excretion was about three times lower and we found influences on diastereoselectivity of (OH)2 -climbazole formation using a modified analytical method. After dermal application, urinary concentration maxima occurred considerably later than after oral intake. The two different dermal exposure scenarios also revealed a relevance of exposure duration and product formulation on the systemic availability of climbazole. Back-calculated oral-dose-equivalent intakes from the dermal exposures showed a maximum climbazole intake of 18.5 µg/kg bw/d after hair tonic use, or 6.6 µg/kg bw/d after AD shampoo application., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gabriele Leng reports financial support was provided by Chemie Wirtschaftsförderungsgesellschaft mbH. Holger M. Koch reports financial support was provided by Chemie Wirtschaftsförderungsgesellschaft mbH. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF