Khellin and
khelloside (khellol
glucoside) were examined in female cynomolgus monkeys to substantiate their ability to favorably modify serum
lipoprotein cholesterol. Clinical chemistry parameters were also measured to obtain information indicative of possible
drug toxicity. Both drugs were evaluated in two week multiple-dose studies and after a single oral dose. After two weeks at 20 mg/kg per day,
khellin and
khelloside significantly lowered
low density lipoprotein cholesterol (
LDL-C) by 87% and 73%,
high density lipoprotein cholesterol (HDL-C) by 41% and 23%, and total-C by 55% and 44%, respectively.
Very low density lipoprotein cholesterol (VLDL-C) and
triglycerides (TG) were not changed. No apparent toxicity was observed as clinical chemistry parameters and
body weights were not different compared to control values. Similar results were observed with lower doses of
khellin and
khelloside.
Khellin at 5 mg/kg per day reduced
LDL-C by 50%, HDL-C by 15%, and total-C by 30%, while khellol
glucoside at 10 mg/kg per day lowered
LDL-C by 46%, HDL-C by 20%, and total-C by 31%. Neither
drug produced significant changes in VLDL-C, TG,
body weights, or clinical chemistry variables. A 2 mg/kg per day dose of
khellin also had no observable effect in this study. Single oral doses (20 mg/kg) of
khellin and
khelloside caused modulation of
LDL-C (-32% and -30%) and total-C (-18% and -15%). Visual observation of the monkeys during this study revealed that
khellin caused
emesis in 9/9 animals, while
khelloside and control had no
emetic effect.(ABSTRACT TRUNCATED AT 250 WORDS)