Phototoxicity of new psoralen-containing gels and creams versus bath PUVA.

BACKGROUND: Bath-PUVA-photochemotherapy has become a useful alternative to oral PUVA therapy due to a number of advantages over systemic PUVA, for example, no ophthalmologic risk and nausea, and a lower cumulative UVA doses. However, its major disadvantage is the logistical requirement for bath tubs in practice and some patients feel uncomfortable to share the same bath with others. Topical psoralen contained preparation may be a good candidate for safe, convenient, and useful regimen in the topical PUVA therapy. OBJECTIVES: The purpose of the present study was to investigate the intensity of the phototoxic response of 8-MOP bath solution to different concentrations of preparations of 8-MOP gels and creams. MATERIAL AND METHOD: Following informed consent, the test bath solution (0.375%), gels (0.0025% to 0.010%) and creams (0.0025% to 0.010%) were applied to the normal-appearing skin of the upper back of 23 volunteers who had no history of photosensitivity. The escalating UVA doses (0.25 to 7.0 J/cm2) were given 15 minutes after application of test substances. Seventy-two hours after UVA exposure minimal phototoxic doses (MPD) were defined visually and the intensity of the erythema response was also assessed by using a narrowband spectrophotometer The MPD and the dose-response curves for erythema response of the gels and creams were compared with those of the bath. RESULTS: There were no significant differences between the overall mean MPD of tested gels and that of bath solution (p > 0.05). On the contrary, the cream preparations induced phototoxic response (MPDs) to a lesser degree than bath solution and gels (p < 0.05). When comparing the slope of the dose-response curve for erythema of 0.0025% and 0.0100% gel to that of the bath solution, the correlation is very strong (R2 = 0.987 and 0.936, respectively, p < 0.0001). CONCLUSION: The present study shows that the threshold of phototoxic response of 0.0025% 8-MOP gel indicated by MPD is well correlated with those of the bath solution. The slope of the dose-response curve for erythema of this preparation also significantly corresponded to that of the bath solution. Thus, the penetration and drug delivery of 0.0025% 8-methoxypsoralen gel may be similar to 8-methoxypsoralen bath solution. This preparation may be a good candidate for a useful therapeutic modality for topical PUVA therapy, and further clinical trial should be performed.

Uso sistémico y tópico de 5-metoxipsoralen: repigmentación del vitiligo con 5-MOP tópico

El vitiligo es una hipomelanosis y amelanosis idiopática adquirida de la piel que afecta un alto porcentaje de la población. La fotoquimioterapia estimula la melanogénesis, la proliferación y la migración de melonocitos. Estudios recientes han mostrado exelente repigmentación con PUVA empleando 5-Metoxipsoralen oral. Este método tiene la ventaja de que produce muy poca fototoxicidad cutánea y náuseas. Hemos tratados 30 pacientes de vitiligo localizado con fotoquimioterapia tópica, empleando una preparación líquida nueva de 5-Metoxipsoralen que ha mostrado ser efectiva en la repigmenación de un número substancial de pacientes. (76.6%)

Study of the skin concentrations after administration of the various phototoxic drugs

The skin concentrations of 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), and 4, 5', 8-trimethylpsoralen (TMP) were studied in the guinea pig following oral administration and bathing. The skin concentration of phototoxic drugs after oral administration peaked at 1.5 hours, and the concentration of 8-MOP was 3.5 times greater than that of 5-MOP. The skin concentration of TMP was not detected in our study (limit of sensitivity 5ng/ml). The skin concentrations of phototoxic drug after bathing decreased in the order of 5-MOP, TMP, and 8-MOP