Formation of a perbenzoic acid derivative in the photodegradation of fenofibrate: phototoxicity studies on erythrocytes.

Abstract

The phototoxic antihyperlipoproteinemic drug fenofibrate (1) is photolabile under aerobic conditions. Irradiation of a methanol solution of 1 produces, under oxygen, photoproducts 2, 3, and 4. A peroxidic photoproduct 2 was isolated and identified. The biologically active antioxidants glutathione and cysteine efficiently reduce 2 to its acid. This photoproduct was also capable of efficiently oxidizing tetramethyl phenylendiamine (TMP) through an electron transfer mechanism, detecting a TMP+ species by UV-visible spectrometry. Fenofibrate was screened in vitro at different concentrations for UV-visible-induced phototoxic effects in a photohemolysis test, under oxygen as well as argon. The photohemolysis rate was low under anaerobic conditions. No hemolysis occurred without irradiation. The isolated photoproduct 2 induced hemolysis without irradiation.

• Authors: F Vargas, C Rivas, N Canudas
• Journal: Journal of pharmaceutical sciences (J Pharm Sci) Vol. 82 Issue 6 Pg. 590-1 (Jun 1993) ISSN: 0022-3549 [Print] United States
• PMID: 8331531 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chlorobenzoates
• 4-chlorobenzoic acid
• Oxygen
• Fenofibrate

Topics

• Chlorobenzoates (chemical synthesis, pharmacology)
• Erythrocytes (drug effects, radiation effects)
• Fenofibrate (radiation effects)
• Hemolysis (drug effects)
• Humans
• Magnetic Resonance Spectroscopy
• Oxygen
• Photochemistry
• Spectrophotometry, Infrared
• Spectrophotometry, Ultraviolet
• Ultraviolet Rays