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.
