Single- and repeated-dose toxicity studies on the novel HIV maturation inhibitor QF-036 in Sprague-Dawley rats

Abstract

QF-036 is a novel human immunodeficiency virus (HIV) maturation inhibitor that is a lupine triterpenoid derivative. The objective of this study was to evaluate the safety of QF-036. A single oral toxicity and a 4-week repeated oral toxicity were investigated in Sprague-Dawley (SD) rats. The single oral toxicity study of QF-036 in SD rats showed that no mortality or visible pathological changes were noted at doses of 100, 300, and 1000 mg/kg. QF-036 exhibited a non-linear toxicokinetic profile over the dose range of 100-1000 mg/kg in the single dose study, and a saturation trend appeared at doses of 100 and 300 mg/kg. In the 4-week oral toxicity and toxicokinetic study, SD rats were given 0, 50, 100, and 200 mg/kg QF-036 once daily for 4 weeks, followed by a 4-week recovery period. No mortality or significant effects on food consumption, body weight, or behavior were observed. In addition, there were no test article-related changes in hematology, clinical biochemistry and histopathology. The no observed adverse effect level (NOAEL) was 200 mg/kg. The toxicokinetic study demonstrated a dose-dependent increase in the systemic exposure to QF-036 after 4 weeks of oral administration. There were no marked sex differences or drug accumulation observed for repeated doses of QF-036.

Keywords: Acute toxicity; HIV maturation; Lupine triterpenoid; QF-036; Repeat dose toxicity; SD rats; Toxicokinetic study.