Photobinding of chlorpromazine and its sulfoxide in vitro and in vivo.

Abstract

Abstract— Photosensitivity as observed after chlorpromazine (CPZ) treatment is enhanced in the UVA‐ rather than the UVB region, whereas CPZ has its absorption maximum at 305 nm. This long wavelength sensitivity has sometimes been ascribed to CPZ‐sulfoxide (CPZSO) which has an absorption maximum at 340 nm. We compared the photobinding properties of CPZSO and CPZ under both in vitro and in vivo conditions.With 310 and 370 nm lamps CPZSO absorbs twice as much light as CPZ but still binds less efficiently to HSA in vitro. At wavelengths longer than 380 nm CPZSO does not absorb nor photobind to HSA (420 nm lamps) in contrast to CPZ. In vivo the bioavailability of CPZ and CPZSO in ears, eyes and skin of the back of Wistar rats is comparable, yet irradiation with 370 nm light caused more CPZ‐photobinding in these tissues. Chlorpromazine binds relatively more compared to CPZSO, to constituents of deeper lying tissues (dermis). This corresponds with the observation that both the ratio of in vitro CPZ photobinding to CPZSO photobinding, and the penetrating ability of light in the skin increase with wavelength.In the eyes, where the lens efficiently filters out light with wavelengths shorter than 370 nm, no CPZSO photobinding was observed, in contrast to CPZ; this also corresponds with the in vitro experiments. Therefore it seems more likely that the observed wavelength maximum in the photosensitivity action spectrum after CPZ treatment should be attributed to the non‐sulfoxidated drug rather than to the sulfoxidated compound.