Pre-clinical toxicity evaluation of MB-102, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate

Regulatory Toxicology and Pharmacology : RTP
Joseph E Bugaj, Richard B Dorshow

Abstract

The fluorescent tracer agent 3,6-diamino-2,5-bis{N-[(1R)-1-carboxy-2-hydroxyethyl]carbamoyl}pyrazine, designated MB-102, has been developed with properties and attributes for use as a direct measure of glomerular filtration rate (GFR). In comparison to known standard exogenous GFR agents in animal models, MB-102 has demonstrated an excellent correlation. A battery of toxicity tests has been completed on this new fluorescent tracer agent, including single dose toxicity studies in rats and dogs to determine overall toxicity and toxicokinetics of the compound. Blood compatibility, mutation assay, chromosomal aberration assay, and several other assays were also completed. Toxicity assessments were based on mortality, clinical signs, body weight, food consumption and anatomical pathology. Doses of up to 200-300 times the estimated human dose were administered. No test-article related effects were noted on body weight, food consumption, ophthalmic observations and no abnormal pathology was seen in either macroscopic or microscopic evaluations of any organs or tissues. All animals survived to scheduled sacrifice. Transient discoloration of skin and urine was noted at the higher dose levels in both species as expected from a highly flu...Continue Reading

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Citations

Jul 6, 2016·European Journal of Pharmacology·Jiaguo HuangStefanie Weinfurter
May 13, 2018·Journal of Biomedical Optics·Martin P Debreczeny, Richard B Dorshow
May 3, 2019·Current Opinion in Nephrology and Hypertension·Sook H ParkLorenzo Gallon
Sep 28, 2017·Current Opinion in Critical Care·Richard Solomon, Stuart Goldstein
Apr 29, 2020·American Journal of Veterinary Research·Christopher G PirieRichard B Dorshow
Aug 11, 2017·ChemistryOpen·Jiaguo Huang, Norbert Gretz
Jan 10, 2018·Anaesthesia·J McKinlayL G Forni
Sep 9, 2017·Scientific Reports·Richard B DorshowPhillip I Tarr
Nov 13, 2019·Journal of Pharmaceutical Sciences·Jeng-Jong ShiehRichard B Dorshow
Oct 2, 2020·Current Opinion in Critical Care·Antoine G Schneider, Bruce A Molitoris

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