CAUTION: METHOXSALEN IS A POTENT DRUG. READ ENTIRE BROCHURE PRIOR TO PRESCRIBING OR DISPENSING THIS MEDICATION.
8-MOP (Methoxsalen, 8-Methoxypsoralen) Capsules, 10mg. Methoxsalen is a naturally occurring photoactive substance found in the seeds of the Ammi majus (Umbelliferae) plant and in the roots of Heracleum Candicans. It belongs to a group of compounds known as psoralens, or furocoumarins. The chemical name of methoxsalen is 9-methoxy-7 H-furo[3,2-g]-benzopyran-7-one; it has the following structure:
II. CLINICAL PHARMACOLOGY
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 melanocyctes 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 at., 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.