Universitas Indonesia Conferences, Asian Federation for Pharmaceutical Sciences (AFPS) 2019

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Photosafety testing: the combination use of photoreactivity and skin deposition
Yosuke Iyama, Hideyuki Sato, Yoshiki Seto, Satomi Onoue

Last modified: 2019-06-15


Background: Drug-induced phototoxicity is an unfavorable skin reaction, and development of reliable screening strategy has been required.

Objective: This study aimed to establish a photosafety testing with use of a reactive oxygen species (ROS) assay and in vitro skin permeation test using Strat-M®, an artificial membrane.

Materials and Methods: Acridine (ACD), furosemide (FSM), hexachlorophene (HCP), 8-methoxypsoralen (MOP), norfloxacin (NFX), and promethazine (PMZ) were selected as test compounds, and the ROS assay was undertaken to evaluate photoreactivity of test compounds.  To calculate steady-state concentration (Css), the in vitro skin permeation test was conducted on test compounds (1 mg/mL) using intact and methanol pre-treated Strat-M®.

Results: All tested compounds generated significant ROS under exposure to simulated sunlight, and the photoreactivity of ACD and HCP were higher than those for other 4 compounds.  The Css values of ACD, FSM, HCP, MOP, NFX, and PMZ were calculated to be 23.4, 19.6, 20.5, 9.4, 5.9, and 38.1 mg/mL, respectively.  The order of Css values in the Strat-M® was mostly in agreement with that in the dissected rat skin, suggesting the applicability of the in vitro skin permeation test with use of the Strat-M® as an alternative methodology.  Based on both ROS and Css data of test compounds, the phototoxic risk was ranked as follows: ACD>HCP>PMZ>FSM>MOP>NFX.  The predicted phototoxic risk by the proposed screening system relatively corresponded to observed in vivo phototoxicity based on the colorimetrical changes in the rat skin (ACD≒HCP>PMZ>MOP>FSM>NFX).

Conclusion: The photosafety assessment, consisting of the ROS assay and in vitro skin permeation test using artificial membranes, would contribute to implementation of animal welfare and reliable photosafety prediction.