"The U.S. Food and Drug Administration today approved Cosentyx (secukinumab) to treat adults with moderate-to-severe plaque psoriasis.
Psoriasis is a skin condition that causes patches of skin redness and irritation. Psoriasis is"...
The combination treatment regimen of psoralen (P) and ultraviolet radiation of 320–400 nm wavelength commonly referred to as UVA is known by the acronym, PUVA. Skin reactivity to UVA (320–400 nm) radiation is markedly enhanced by the ingestion of methoxsalen. The drug reaches its maximum bioavailability 1 1/2–3 hours after oral administration and may last for up to 8 hours (Pathak et al. 1974)1. Methoxsalen is reversibly bound to serum albumin and is also preferentially taken up by epidermal cells (Artuc et al. 1979)2. At a dose which is six times larger than that used in humans, it induces mixed function oxidases in the liver of mice (Mandula et al. 1978)3. In both mice and man, methoxsalen is rapidly metabolized. Approximately 95% of the drug is excreted as a series of metabolites in the urine within 24 hours (Pathak et al. 1977)4.
The exact mechanism of action of methoxsalen with the epidermal melanocytes and keratinocytes is not known. The best known biochemical reaction of methoxsalen is with DNA. Methoxsalen, upon photoactivation, conjugates and forms covalent bonds with DNA which leads to the formation of both monofunctional (addition to a single strand of DNA) and bifunctional adducts (crosslinking of psoralen to both strands of DNA) (Dall'Acqua et al., 19715; Cole, 19706; Musajo et al., 19747; Dall'Acqua et al., 19798). Reactions with proteins have also been described (Yoshikawa, et al., 19799).
Methoxsalen acts as a photosensitizer. Administration of the drug and subsequent exposure to UVA can lead to cell injury. Orally administered methoxsalen reaches the skin via the blood and UVA penetrates well into the skin. If sufficient cell injury occurs in the skin, an inflammatory reaction occurs. The most obvious manifestation of this reaction is delayed erythema, which may not begin for several hours and peaks at 48–72 hours. The inflammation is followed, over several days to weeks, by repair which is manifested by increased melanization of the epidermis and thickening of the stratum corneum. The mechanisms of therapy are not known. In the treatment of vitiligo, it has been suggested that melanocytes in the hair follicle are stimulated to move up the follicle and to repopulate the epidermis (Ortonne et al, 197910). In the treatment of psoriasis, the mechanism is most often assumed to be DNA photodamage and resulting decrease in cell proliferation but other vascular, leukocyte, or cell regulatory mechanisms may also be playing some role. Psoriasis is a hyperproliferative disorder and other agents known to be therapeutic for psoriasis are known to inhibit DNA synthesis.
1. Pathak, M. A., Kramer, D. M., Fitzpatrick, T. B.: Photobiology and Photochemistry of Furocoumarins (Psoralens), SUNLIGHT AND MAN: Normal and Abnormal Photobiologic Responses. Edited by M. A. Pathak, L. C. Harbor, M. Seiji et al. University of Tokyo Press. 1974, pp. 335-368.
2. Artuc, M., Stuettgen, G., Schalla, W., Schaefer, H., and Gazith, J.: Reversible binding of 5- and 8-methoxypsoralen to human serum proteins (albumin) and to epidermisin vitro:Brit. J. Dermat. 101, pp. 669-677 (1979).
3. Mandula, B. B., Pathak, M. A., Nakayama, Y., and Davidson, S. J.: Induction of mixed-function oxidases in mouse liver by psoralens, Ibid, 99, pp. 687-692 (1978).
4. Pathak, M. A., Fitzpatrick, T. B., Parrish, J. A.: PSORIASIS, Proceedings of the Second International Symposium. Edited by E. M. Farber, A. J. Cox, Yorke Medical Books, pp. 262–265 (1977).
5. Dall'Acqua, F., Marciani, S., Ciavatta, L., Rodighiero, G.: Formation of interstrand cross-linkings in the photoreactions between furocoumarins and DNA; Z Naturforsch (B), 26, pp. 561–569 (1971).
6. Cole, R. S.: Light-induced cross-linkings of DNA in the presence of a furocoumarin (psoralen), Biochem. Biophys. Acta. 217, pp. 30–39 (1970).
7. Musajo, L., Rodighiero, G., Carporale, G., Dall'Acqua, F., Marciani, S., Bordin, F., Baccichetti, F., Bevilacqua, R.: Photoreactions between Skin-Photosensitizing Furocoumarins and Nucleic Acids, SUNLIGHT AND MAN; Normal and Abnormal Photobiologic Responses. Edited by M. A. Pathak, L. C. Harber, M. Seiji et al., University of Tokyo Press, pp. 369–387 (1974).
8. Dall'Acqua, F., Vedaldi, D., Bordin, F., and Rodighiero, G.: New studies in the interaction between 8-methoxypsoralen and DNA in vitro; J. Investigative Dermat., 73, pp. 191–197 (1979).
9. Yoshikawa, K., Mori, N., Sakakibara, S., Mizuno, N., Song, P.: Photo-Conjugation of 8-methoxypsoralen with Proteins,Photochem & Photobiol. 29, pp. 1127–1133 (1979).
10. Ortonne, J. P., MacDonald, D. M., Micoud, A., Thivolet, J.: PUVA-induced repigmentation of vitiligo: a histochemical (split-DOPA) and ultra-structural study: Brit. J. of Dermat., 101, pp. 1–12 (1979).
Last reviewed on RxList: 12/15/2008
This monograph has been modified to include the generic and brand name in many instances.
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