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• W2945344467 abstract "The present study aimed to develop a photochemically stabilized formulation of dacarbazine [5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide; DTIC] for reducing the production of algogenic photodegradant (5-diazoimidazole-4-carboxamide; Diazo-IC). Photochemical properties of DTIC were characterized by UV-visible light spectral analysis, reactive oxygen species (ROS) assay, and photostability testing. A pharmacokinetic study was conducted after intravenous administration of DTIC formulations (1 mg-DTIC/kg) to rats. DTIC exhibited strong absorption in the UVA range, and photoirradiated DTIC exhibited marked ROS generation. Thus, DTIC had high photoreactive potential. After exposure of DTIC (1 mM) to simulated sunlight (250 W/m2) for 3 min, remaining DTIC and yielded Diazo-IC were estimated to be ca. 230 μM and 600 μM, respectively. The addition of radical scavenger (1 mM), including l-ascorbic acid, l-cysteine (Cys), l-histidine, D-mannitol, l-tryptophan, or l-tyrosine, to DTIC (1 mM) could attenuate DTIC photoreactions, and in particular, the addition of Cys to DTIC brought ca. 34% and 86% inhibition of DTIC photodegradation and Diazo-IC photogeneration, respectively. There were no significant differences in the calculated pharmacokinetic parameters of DTIC between DTIC and DTIC with Cys (0.67 mg/kg). From these findings, the supplementary use of Cys would be an effective approach to improve the photostability of DTIC with less production of Diazo-IC." @default.
• W2945344467 created "2019-05-29" @default.
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• W2945344467 date "2019-06-01" @default.
• W2945344467 modified "2023-09-26" @default.
• W2945344467 title "Photochemically stabilized formulation of dacarbazine with reduced production of algogenic photodegradants" @default.
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• W2945344467 doi "https://doi.org/10.1016/j.ijpharm.2019.04.063" @default.
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