title: Penetration of lycopsamine from a comfrey ointment through human epidermis.
abstract: Mutagenic and teratogenic pyrrolizidine alkaloids (PAs) have been identified in several plant species. The industrially most important PA-containing plant is Symphytum officinale (common comfrey). The application of its root is restricted in several countries due to its PA content. In medicines, the daily alkaloid quantity and duration of treatment may be limited even in case of topical application. Due to the confirmed good absorption of PAs from the gastrointestinal tract, the prohibition of oral use is justified, however the limitation of external application is not supported by relevant data. Penetration experiments on human skin are not available to be a rational basis for limitation. The aim of our work was to carry out pharmacokinetic studies on the diffusion and penetration of lycopsamine (a main PA of comfrey) from a Symphytum product through a synthetic membrane and human skin. Investigations were carried out on vertical Franz diffusion cell and lycopsamine was quantified by a validated LC-MS method. The amount of lycopsamine diffused through a synthetic membrane varied between 0.11% and 0.72% (within 24 h). On human epidermis, the rate of penetration was lower (0.04-0.22%). Our results may contribute to the more realistic toxicological assessment of externally applied PA-containing products.
authors.affiliation: University of Szeged, Faculty of Pharmacy, Department of Pharmacognosy, H-6720, Szeged, Eötvös Street 6, Hungary.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Jedlinszki
authors.affiliation: University of Szeged, Faculty of Pharmacy, Department of Pharmaceutical Technology, H-6720, Szeged, Eötvös Street 6, Hungary.
authors.forename: Boglárka
authors.initials: B
authors.lastname: Balázs
authors.affiliation: University of Szeged, Faculty of Pharmacy, Department of Pharmaceutical Technology, H-6720, Szeged, Eötvös Street 6, Hungary.
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Csányi
authors.affiliation: University of Szeged, Faculty of Pharmacy, Department of Pharmacognosy, H-6720, Szeged, Eötvös Street 6, Hungary; Interdisciplinary Centre of Natural Products, University of Szeged, Eötvös u. 6, H-6720, Szeged, Hungary. Electronic address: csupor.dezso@pharmacognosy.hu.
authors.forename: Dezső
authors.initials: D
authors.lastname: Csupor
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D020844:Comfrey / Q000737:chemistry*; D004058:Diffusion; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D008567:Membranes, Artificial; D008954:Models, Biological; D009824:Ointments; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000378:metabolism* / Q000633:toxicity; D018517:Plant Roots; D010946:Plants, Medicinal; D011763:Pyrrolizidine Alkaloids / Q000008:administration & dosage / Q000302:isolation & purification / Q000378:metabolism* / Q000633:toxicity; D018570:Risk Assessment; D012869:Skin Absorption; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D066007:Toxicokinetics
chemical_list: D008567:Membranes, Artificial; D009824:Ointments; D010936:Plant Extracts; D011763:Pyrrolizidine Alkaloids; C018336:indicine
keywords: Absorption; Comfrey; Epidermis; Franz diffusion cell; Lycopsamine; Pyrrolizidine alkaloid; Skin