Triprolidine and the Response of Skin to Ultra-Violet Radiation.

Abstract

interest has been aroused by reports that triprolidine HCl (Actidil, Pro-Actidil) will abolish the abnormal responses to sunlight in photosensitive patients (Loewenthal, 1963a) and reduce significantly the sunburn reaction in normal subjects (Loewenthal, 19636). These observations are potentially of very great importance for it may be that an agent which suppresses the acute effects of ultraviolet radiation (U.V.R.) in the skin may be capable of preventing the chronic effects, especially neoplasia. (For a review of carcinogenesis by U.V.R. see Blum, 1961). In view of this and of the interest aroused, as shown by an annotation in the British Medical Journal (1963) and notice in the lay press, Loewenthal's report merits confirmation. We have, therefore, studied some of the more acute effects of U.V.R. on the skin of subjects treated with triprohdine by (i) examining the normal erythemal response with and without the drug in (a) humans and (b) mice ; (ii) seeking alteration by the drug of pathological responses in patients abnormally photosensitive, and (iii) assaying the protection afforded by topical triprolidine on human skin. INVESTIGATION.A 2 kW. high pressure zenon arc source with a quartz envelope was used to provide radiation of wide spectrum very similar to sunlight and also as a source for an irradiation monochromatoi-. The latter, a quartz instrument (Magnus et al., 1959), provided radiation at 300 m/x, a wavelength which produces an easily measurable minimal erythemal dose (M.E.D.) in normal subjects, and is strongly absorbed by a 1% aqueous solution of triprolidine hydrochloride (Loewenthal, 1963a).As the strong continuum of the xenon arc includes radiation of shorter wavelength than that found in terrestial sunlight, a cut-off filter (Schott WG6, 3mm. thickness) was placed between the arc and the skin when radiation approximating to midday summer sunlight (Wiskemann and Wulf, 1956) was required.Intensity was measured with a calibrated thermopile. U.V. dosage is expressed as the product of length of exposure (seconds) and intensity (^nW/cm^). The dose values should be regarded as relative rather than absolute.(i) Monochromatic irradiation of normal skin.-(a) Normal subjects were irradiated on the back with 300 m/it U.V.R. Adjoining areas of skin on each subject were exposed to 1, 2, 4, 8, 15, 30 and 60 second doses and examined at approximately 3, 7, 11, 13 and 24 hours afterwards to determine the M.E.D. The test was then repeated 48 hours later, after 9 subjects had taken two sets of tablets, one set being the longacting triprolidine (20 mg. Pro-Actidil), the other the short-acting triprolidine (5 mg. Actidil). The long-acting triprolidine was swallowed at 10 p.m. the evening before, followed by the short-acting tablets lj to 2 hours before retesting the M.E.D. at about