Plasma levels of 8‐methoxypsoralen following PUVA‐bath photochemotherapy

Abstract

Administration of 8-methoxypsoralen (8-MOP) in a dilute bath water solution is an effective therapeutic alternative to oral PUVA therapy, avoiding systemic side effects, offering better bioavailability of the psoralen and requiring much smaller amounts of UVA for induction of therapeutic effects. To obtain exact data about the percutaneous absorption of 8-MOP during a psoralen bath, the plasma levels of the drug were determined in 26 patients with different skin diseases by a reverse high-performance liquid chromatographic method. Fifteen patients receiving oral PUVA therapy (0.8 mg 8-MOP/kg body weight) served as a positive control group. Bath solutions were prepared by diluting 15 ml of 0.5% stock solution of 8-MOP in 150 l of bath water (0.5 mg/l, 37 degrees C). Blood samples were drawn from patients 5, 30, 60, 120 and 180 min after the bath. In the oral PUVA group, blood samples were obtained 1 1/2 h after administration of the drug. In 23 of 26 patients, 8-MOP levels were undetectable in every blood sample. After 30 min, two patients showed detectable levels of 8-MOP (5 ng/ml, 7 ng/ml), while 60 min after the PUVA bath 8-MOP was detectable in only one volunteer (5 ng/ml). In patients receiving oral 8-MOP therapy, serum levels varied between 45 and 360 ng/ml 1 1/2 h after drug administration. Our data confirm extremely low 8-MOP levels resulting from 8-MOP bath water treatments and provide confirmation of the absence of systemic side effects in patients who are undergoing PUVA-bath therapy.

Treatment of Genito-Anal Lesions in Inflammatory Skin Diseases with PUVA Cream Photochemotherapy: An Open Pilot Study in 12 Patients

“…Recently, PUVA bath photochemotherapy has been proven highly effective in the treatment of a number of inflammatory skin diseases, including localized scleroderma [3, 4]. In contrast to oral PUVA that is often limited by systemic side-effects such as nausea, vomiting and persistent photosensitization of the entire skin and cornea, topical PUVA proved to be exceedingly well tolerated by patients because of the negligible systemic absorption of psoralen [5]. A special form of topical PUVA therapy using 8-methoxypsoralen (8-MOP)-containing cream [6]or gel preparations has been demonstrated to be as effective as PUVA bath therapy for palmoplantar dermatoses [7].…”

A Quantitative Mass Spectrometry-Based Approach for Assessing the Repair of 8-Methoxypsoralen-Induced DNA Interstrand Cross-Links and Monoadducts in Mammalian Cells

“…It is worth noting that 8-MOP could be rapidly absorbed after oral administration or penetrates into the epidermis and dermis following topical (cream or bath) application. The peak concentrations of 8-MOP in patient plasma and dermis are in the range of 45–970 ng/mL, 29–31 and the UVA dose employed for PUVA treatment is typically within the range of 1–10 J/cm 2 32, 33 . Thus, the concentration of 8-MOP (2.5 μM, or 540 ng/mL) and the dose of UVA irradiation (2 J/cm 2 ) used in this study were pharmacologically relevant.…”

High Plasma Levels of 8-Methoxypsoralen following Bath Water Delivery in Dermatological Patients

“…According to von Kobyletzki et al [5], only 2 of 26 patients showed detectable levels of 8-MOP (5 and 7 ng/ml) 30 min after bath therapy (0.5 mg 8-MOP/l water). After oral PUVA therapy (0.8 kg 8-MOP/kg body weight), serum levels varied between 45 and 360 ng/ml 1.5 h after drug administration.…”

“…According to the literature systemic 8-MOP levels from Kappes/Barta/Merkel/Balogh/Elsner skin absorption after bath PUVA are basically low to undetectable; however, exceptions have been described [5][6][7][8]. Therefore it was of interest to investigate the bioavailability of 8-MOP absorbed through the skin in bath PUVA therapy.…”