Abstract 4915: Preclinical pharmacology and toxicology of intravenous BPM31510, a coenzyme Q10-containing lipid nanodispersion

Abstract

Abstract Coenzyme Q10 (CoQ10) plays an important role in cellular metabolism with redox capabilities beyond the mitochondria. Although, the role of CoQ10 in providing benefit in diseases such as cardiovascular, neurodegeneration, and cancer is well established, it has been limited by the absence of delivery methods to achieve physiologically relevant bio-availability. BPM31510 is a CoQ10 (ubidecarenone) containing lipid nanodispersion that delivers supraphysiological concentrations of CoQ10 to tissues, cells and mitochondria. BPM31510 is currently in clinical trials for the treatment of solid tumors including pancreatic cancer and glioblastoma multiforme. This study describes the preclinical pharmacokinetic (PK) and toxicokinetic assessment of BPM31510 (62.5, 125, and 250 mg/kg) after acute (single) intravenous (IV) administration and chronic (3 times a week for 4 weeks), and after a two week recovery from the last exposure in rats. Here, it was demonstrated that the formulation enables an effective delivery of CoQ10 with a robust increase in plasma level and dose-dependent accumulation in several tissues. PK analysis of mean plasma concentration of CoQ10 after a single and repeat dose administration revealed a dose proportion effect on peak (Cmax) and total exposure (AUC0-t). Tissue analysis of CoQ10 levels demonstrates a dose-dependent increase in liver, lung and pancreas 72 hours post-last dose. A dose dependent elimination was observed in both male and females. No difference in pharmacokinetic of CoQ10 using this formulation was observed between males and females. Notably, chronic exposure to BPM31510 does not lead to toxicities as assessed by hematology and coagulation, clinical chemistry, histopathology and gross necropsy. These results indicate that the effective delivery and bioavailability of supraphysiological levels of CoQ10 after IV administration of BPM31510 is well tolerated. Citation Format: David Linsenmayer, Shiva Kazerounian, Khampaseuth Thapa, Carrie Spencer, Aishwarya Sarma, John McCook, Stephane Gesta, Vivek Vishnudas, Niven R. Narain, Rangaprasad Sarangarajan. Preclinical pharmacology and toxicology of intravenous BPM31510, a coenzyme Q10-containing lipid nanodispersion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4915.