Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Tiffner, KI; Ramezanli, T; Boulgaropoulos, B; Birngruber, T; Bodenlenz, M; Lackner, BC; Raml, R; Jiang, Y; Raney, SG; Sinner, F.
Cutaneous pharmacokinetics-based bioequivalence: A clinical dermal open flow microperfusion verification study using lidocaine and prilocaine combination topical products
EUR J PHARM SCI. 2024; 200: 106827
Doi: 10.1016/j.ejps.2024.106827
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Sinner Frank Michael
- Co-Autor*innen der Med Uni Graz
- Birngruber Thomas
- Boulgaropoulos Beate
- Weiss Manfred
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- Abstract:
- BACKGROUND: Using accurate, sensitive, reproducible and efficient in vivo cutaneous pharmacokinetics (PK)-based bioequivalence (BE) approaches can promote the development of topical generic products. A clinical dermal open flow microperfusion (dOFM) study has previously demonstrated the BE of topical drug products containing a hydrophilic drug. However, the utility of dOFM to evaluate the topical BE of drug products containing moderately lipophilic drugs, more representative of most topical drugs, has not yet been established. OBJECTIVE: To evaluate the ability of a clinical dOFM study to assess BE of topical products containing two moderately lipophilic drugs that have only minor differences in chemical and physical properties. METHODS: The study included 20 healthy subjects. Four application sites on each thigh were treated with fixed dose lidocaine/prilocaine combination products, and dermal drug concentrations were monitored with two dOFM probes per application site for 12 hours. A reference cream was compared to itself and to an approved generic cream (both serving as positive controls for BE), and to a gel (negative control). BE was established based on AUC0to12h and Cmax using the scaled-average-BE approach. Systemic exposure of both drugs was assessed throughout the study. RESULTS: BE was successfully demonstrated for the positive controls, and not for the negative control, for both drugs. The systemic exposure of both drugs was negligible. CONCLUSIONS: dOFM accurately demonstrated BE between bioequivalent topical creams, sensitively discriminated between different formulations and differentiated the cutaneous PK of both study drugs, even though they differ only slightly in chemical and physical properties. These results support the utility of dOFM as a cutaneous PK BE approach for topical lipophilic drugs, including lidocaine and prilocaine.
- Find related publications in this database (Keywords)
- Bioequivalence
- Dermal open flow microperfusion
- Topical
- Lidocaine
- Prilocaine
- Cutaneous pharmacokinetics