Psoralens form covalent linkages with pyrimidine bases
in DNA when exposed to light of the appropriate wavelength,
and if oxygen is present, reactive oxygen species
also are generated. Although inhibition of DNA replication
may account for some of the beneficial effects of
PUVA therapy in certain hyperproliferative disorders
such as psoriasis, PUVA has other important biological
effects.
Pharmacology
Orally administered psoralens are rapidly absorbed
(maximum photosensitivity for the most common
preparation, 8-methoxypsoralen [Oxsoralen Ultra], is
1–1.5 hours). Although the elimination half-life is 2.2
hours, the skin remains photosensitive for 8 to 12 hours.
Most excretion is renal, and the drug does not accumulate.
It can be absorbed if applied topically, and after
application to the entire body, therapeutic plasma levels
can be detected.
Clinical Use
It suppresses contact hypersensitivity and may
evoke other immunological changes by affecting T lymphocytes
and epidermal Langerhans cells. It increases
melanin pigmentation in the skin and is useful in treating
vitiligo. PUVA also inhibits mast cell release of inflammatory
mediators.
