Absence of developmental or reproductive toxicity in rats for MB-102, a fluorescent tracer agent for point-of-care measurement of glomerular filtration rate

Abstract

The fluorescent tracer agent MB-102 was designed for the direct, real-time measurement of glomerular filtration rate. Previous studies, both in vitro and in vivo (rats, rabbits and dogs) have assessed single dose toxicity, phototoxicity, local tolerance, hERG channel changes, mutation, chromosomal aberration, micronuclease assays, and CNS and cardiovascular safety. The resulting safety/toxicology profile allowed FDA clearance to conduct Phase I and II human clinical studies. Herein we report on maternal toxicity and potential effects on embryo-fetal development and toxicokinetics of MB-102 administered daily via intravenous (bolus) injection into pregnant rats during organogenesis gestation day 6–17. Mortality, clinical observations, body weight, food consumption, reproductive performance, necropsy, and cesarean section findings were assessed. Blood samples were evaluated toxicokinetically. No significant findings were noted in any endpoints. The only clinical findings were skin, eye or pelage discoloration in the two higher dose groups, which were considered related to the color and fluorescent properties of MB-102 and deemed non-adverse. Exposure, assessed by Cmax and AUC(0-6), increased in a dose-dependent manner from 9 to 225 mg/kg/day. Thus, intravenous administration of MB-102 was not associated with any adverse developmental or reproductive toxicities in pregnant rats.