In:
Skin Pharmacology and Physiology, S. Karger AG, Vol. 36, No. 3 ( 2023), p. 107-116
Abstract:
〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 The use of epicutaneously applied permethrin in the treatment of common scabies is considered to be the first-line therapy. Due to increasing clinical treatment failure, the development of genetic resistance to permethrin in 〈 i 〉 Sarcoptes scabiei var. hominis 〈 /i 〉 has been postulated. In addition, metabolic resistance and pharmacokinetic limitations by parasitic digestion and reactive thickening of 〈 i 〉 stratum corneum 〈 /i 〉 are suspected to cause a reduction in cutaneous bioavailability. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Since lipophilic permethrin is known to form hydrophobic interactions with proteins via van der Waals interactions, a similar interaction was assumed and investigated for permethrin and the protein keratin. Using keratin particles extracted from animal material, a model for hyperkeratotic and parasitic digested scabies skin was developed. Using fluorescence-labeled keratin and ³H-permethrin, their interaction potential was validated by loading and unloading experiments. Additionally, the impact of keratin to permethrin penetration was investigated based on an in vitro model using Franz diffusion cells. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 For the first time, keratin particles were introduced as a model for dyskeratotic skin, as we were able to show, the keratin particles’ interaction potential with permethrin but no penetration behavior into the 〈 i 〉 stratum corneum 〈 /i 〉 . Moreover, comparative penetration experiments of a reference formulation with and without added keratin or keratin-adherent permethrin showed that keratin causes a steal effect for permethrin, leading to a relevant reduction in cutaneous bioavailability in the target compartment. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 The results provide further evidence for a relevant pharmacokinetic influencing factor in the epicutaneous application of permethrin and a rationale for the necessity of keratolytic pretreatment in hyperkeratotic skin for the effective use of topical permethrin application in scabies.
Type of Medium:
Online Resource
ISSN:
1660-5527
,
1660-5535
Language:
English
Publisher:
S. Karger AG
Publication Date:
2023
detail.hit.zdb_id:
1483572-1
SSG:
15,3
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