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Regul Toxicol Pharmacol. 2018 Dec;100:59-67. doi: 10.1016/j.yrtph.2018.10.009. Epub 2018 Oct 22.

Intravenous toxicity and toxicokinetics of an HDL mimetic, Fx-5A peptide complex, in cynomolgus monkeys.

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National Center for Advancing Translational Sciences, NIH, Rockville, MD, 20850, USA.
National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
National Center for Advancing Translational Sciences, NIH, Rockville, MD, 20850, USA. Electronic address:


Fx-5A peptide complex (Fx-5A), a High Density Lipoproteins (HDL) mimetic, has been shown to reduce atherosclerosis. The safety and toxicokinetics of Fx-5A administered IV by 30 min infusion at 8, 25 or 75 mg/kg body weight or vehicle, once every other day for 27 days, were assessed in cynomolgus monkeys. The Fx-5A was well tolerated at all doses. At the highest dose, there were statistically significant effects on hematology and clinical chemistry parameters that were considered non-adverse. Dose-dependent recoverable non-adverse erythrocytes morphological changes (acanthocytes, echinocytes, spherocytes, microcytes, and/or schistocytes) were observed. Fx-5A was not hemolytic in in-vitro fresh NHP or human blood assay. There were no Fx-5A-related statistically significant changes for any cardiovascular function, ECG or respiratory parameters, when compared to control. In addition, there were no Fx-5A-related effects on organ weights, macroscopic or microscopic endpoints. Finally, Fx-5A exhibited sporadic non-appreciable detection of anti-Fx-5A antibodies and a dose-dependent linear toxicokinetics with T1/2 value ranges from 2.7 to 6.2 h. In conclusion, the No Observed Adverse Effect Level was considered to be 75 mg/kg/day with associated exposures average Cmax and AUC0-last of 453 μg/mL and 2232 h μg/mL, respectively, on Day 27.


Atherosclerosis; Cynomolgus monkeys; Fx-5A peptide complex; HDL mimetic; Safety

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