Combined use of in vitro phototoxic assessments and cassette dosing pharmacokinetic study for phototoxicity characterization of fluoroquinolones.

The present study aimed to develop an effective screening strategy to predict in vivo phototoxicity of multiple compounds by combined use of in vitro phototoxicity assessments and cassette dosing pharmacokinetic (PK) studies. Photochemical properties of six fluoroquinolones (FQs) were evaluated by UV spectral and reactive oxygen species (ROS) assays, and phototoxic potentials of FQs were also assessed using 3T3 neutral red uptake phototoxicity test (3T3 NRU PT) and intercalator-based photogenotoxicity (IBP) assay. Cassette dosing pharmacokinetics on FQs was conducted for calculating PK parameters and dermal distribution.

High-throughput screening system for identifying phototoxic potential of drug candidates based on derivatives of reactive oxygen metabolites.

Purpose: The present study aimed to develop a high-throughput screening strategy for predicting the phototoxic potential of pharmaceutical substances, using a derivatives-of-reactive-oxygen-metabolites (D-ROM) assay.

Methods: The assay conditions of the D-ROM assay were optimized with a focus on screening run time, sensitivity, solvent system, and reproducibility. The phototoxic potentials of 25 model compounds were assessed by the D-ROM assay, as well as by other screening systems for comparison, including the reactive oxygen species (ROS) assay, the DNA-photocleavage assay, and the 3T3 neutral red uptake phototoxicity test (3T3 NRU PT).

Drug-induced phototoxicity; an early in vitro identification of phototoxic potential of new drug entities in drug discovery and development.

Drug-induced photoirritation can be defined as an inflammatory reaction of the skin after topical or systemic administration of pharmaceutical substances. In many cases of drug-induced phototoxicity, skin reactions can be triggered by doses of sunlight regarded as harmless and most often in the ultraviolet A (320-400 nm). Several classes of drugs including antibacterials, thiazide diuretics, non-steroidal anti-inflammatory drugs, quinolones, and tricyclic antidepressants, even though nontoxic by themselves, may become reactive under exposure to environmental light, leading to undesired side effects.