Analytical Studies on the Prediction of Photosensitive/Phototoxic Potential of Pharmaceutical Substances

Onoue, Satomi; Tsuda, Yoshiko

doi:10.1007/s11095-005-8497-9

Cited by 114 publications

(85 citation statements)

References 29 publications

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“…9 Quinine did not generate any ROS as long as it was protected from light, whereas photoirradiated quinine exhibited the generation of ROS and both singlet oxygen and superoxide anion in concentration-and time-dependent manners. 9 Singlet oxygen reacts rapidly with proteins, 19,20 and interacts with them via two pathways; (1) physical quenching results in energy transfer and de-excitation of the singlet state without any chemical change in the energy acceptor; (2) a chemical reaction results in chemical changes in targets. Irradiated Trp may react with singlet oxygen through both processes which vary with the presence and position of the substituents on the indole ring of Trp.…”

Section: Photochemical Characterization Of Trpmentioning

confidence: 94%

“…9 The screening method we developed would be effective for the assessment of photosensitive/phototoxic potential by determining the generation of reactive oxygen species (ROS). In this investigation, we evaluated the photoreactivity of essential amino acids using the screening method we reported, with the aim being to understand the photochemical properties of Trp, as well as the other essential amino acids.…”

Section: Introductionmentioning

confidence: 99%

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Photoreactivity of Amino Acids: Tryptophan-induced Photochemical Events via Reactive Oxygen Species Generation

2007

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ChemicalsEssential amino acids, quinine, sodium dodecyl sulfate (SDS), and several ROS scavengers, such as butylated hydroxyanisole (BHA), reduced gluthatione (GSH), sodium azide (NaN3), and Tryptophan (Trp), an aromatic amino acid, is a constituent of peptides/proteins and is also a precursor of serotonin, kynurenine derivatives, and nicotinamide adenine dinucleotides. There have been a number of reports on photochemical reactions involving peptides/proteins which contain Trp that showed significant photodegradation, dimerization, and photoionization. The photochemical properties of Trp have not been fully elucidated, and this would provide novel insight into the handling of Trp-containing peptides/proteins. Consequently, we have been trying to evaluate the photochemical properties of Trp, as well as other essential amino acids, focusing on their photosensitivity, photodegradation, and their ability to induce lipid peroxidation. Among all the essential amino acids tested, Trp exhibited the maximal level of superoxide anion generation under 18 h of light exposure (30000 lux). UV spectral analysis of Trp suggested the absorbability of UVA/B light, and exposure of Trp, in both solid and solution states, to UVA/B light resulted in significant photodegradation (t0.5: 18 h) and gradual color changes. In addition, photoirradiated Trp generated lipoperoxidant, a causative agent of photoirritation, and this might be associated with ROS generation.

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Section: Photochemical Characterization Of Trpmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Photoreactivity of Amino Acids: Tryptophan-induced Photochemical Events via Reactive Oxygen Species Generation

2007

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“…2B) since the good relationship between ROS data on chemicals at 200 mM and in vivo phototoxicity revealed the prediction capacity of the ROS assay (Onoue and Tsuda, 2006;Onoue et al, 2008a). FF and FA exhibited potent generation of singlet oxygen, with values of 463 and 531 (DA 440 nm Â 10 3 ), respectively; they also generated superoxide, with values of 171 and 332 (DA 560 nm Â 10 3 ).…”

Section: Resultsmentioning

confidence: 98%

“…Phototoxic reactions can be triggered by photochemical reactions of drug molecules after absorption of UV and visible light (290-700 nm) (Moore, 1998;Onoue and Tsuda, 2006). Herein, the photochemical properties of FF and two major metabolites, FA and RFA, were analyzed with a focus on UVabsorbing properties and ROS-generating potentials.…”

Section: Resultsmentioning

confidence: 99%

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New Photosafety Assessment Strategy Based on the Photochemical and Pharmacokinetic Properties of Both Parent Chemicals and Metabolites

et al. 2015

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Photoreactivity and dermal/ocular deposition of compounds have been recognized as key considerations for evaluating the phototoxic risk of compounds. Because some drugs are known to cause phototoxic reactions via generation of potent phototoxic metabolites, photosafety assessments on parent drugs alone may lead to false predictions about their photosafety. This study aimed to establish a new photosafety assessment strategy for evaluating the in vivo phototoxic potential of both a parent substance and its metabolites. The in vivo phototoxic risk of fenofibrate (FF) and its metabolites, fenofibric acid (FA) and reduced fenofibric acid, were evaluated based on photochemical and pharmacokinetic analyses. FF and FA exhibited intensive UV absorption, with molar extinction coefficient values of 17,000 (290 nm) and 14,000 M 21 cm 21 (295 nm), respectively. Superoxide generation from FA was significantly higher than from FF, and a marked increase in superoxide generation from FF was observed after incubation with rat hepatic S9 fractions, suggesting enhanced photoreactivity of FF after metabolism. FA showed high dermal/ocular deposition after oral administration (5 mg/kg, p.o.) although the concentration of FF was negligible, suggesting high exposure risk from FA. On the basis of these findings, FA was deduced to be a major contributor to phototoxicity induced by FF taken orally, and this prediction was in accordance with the results from in vitro/in vivo phototoxicity tests. Results from this study suggest that this new screening strategy for parent substances and their metabolites provides reliable photosafety information on drug candidates and would be useful for drug development with wide safety margins.

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Photoallergy

DubakienÄ¹

2009

General, Applied and Systems Toxicology

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Photosensitive skin reactions occur when human skin abnormally reacts to ultraviolet radiation or visible light. The forms of photosensitivity are phototoxity and photoallergy. Phototoxic disorders have a high incidence, whereas photoallergic reactions are much less frequent in the human population. Several hundred substances, chemicals or drugs may invoke phototoxic or photoallergic reactions. In order to avoid photosensitive reactions it is essential to determine the photosensitizing properties of such substances before drugs are introduced in therapy or products made available on the market. This chapter reviews the mechanisms of photosensitization, explains the most important differences between phototoxic and photoallergic reactions, summarizes the most common photosensitzers and presents the clinical features and diagnostic procedures of phototoxic and photoallergic reactions.

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Analytical Studies on the Prediction of Photosensitive/Phototoxic Potential of Pharmaceutical Substances

Cited by 114 publications

References 29 publications

Photoreactivity of Amino Acids: Tryptophan-induced Photochemical Events via Reactive Oxygen Species Generation

Photoreactivity of Amino Acids: Tryptophan-induced Photochemical Events via Reactive Oxygen Species Generation

New Photosafety Assessment Strategy Based on the Photochemical and Pharmacokinetic Properties of Both Parent Chemicals and Metabolites

Photoallergy

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