Effect of a synthetic prostaglandin E2 analogue,RS-86505-007, on plasma lipids and lipoproteins in patients with moderate hypercholesterolaemia: efficacy and tolerance of treatment and response in different apolipoprotein polymorphism groups

A double-blind, placebo-controlled ascending dose trial was carried out to evaluate the hypocholesterolaemic efficacy and tolerance of RS-86505-007, a prostaglandin E₂ analogue, in moderately hypercholesterolaemic patients. Twenty-four patients received an oral dose of RS-86505-007 3 g t.i.d. and a separate group of 26 patients 6 g t.i.d. for 6 weeks. Plasma total and low-density lipoprotein (LDL) cholesterol concentrations decreased after 2 weeks of treatment, and the reductions were dose dependent. After 6 weeks of treatment (6 g t.i.d.), the reductions from baseline in total and LDL cholesterol concentration were 14.6% and 18.5%, respectively. No changes in the plasma concentration of triglycerides or high-density lipoprotein (HDL) cholesterol were observed. RS-86505-007 tended to reduce total and LDL cholesterol concentrations less in patients with the 4 allele of the apolipoprotein E than in those with 3 allele. In contrast, the XbaI or EcoRI polymorphisms of the apolipoprotein B gene seemed to have no effect on the hypocholesterolaemic efficacy of the drug. The drug had no effect on the lipoprotein (a) concentration. Sixty-three per cent of patients receiving 3 g t.i.d. and 81% receiving 6 g t.i.d. had adverse events, two-thirds of which related to the gastrointestinal tract. One patient in the 3-g group and three patients in the 6-g group terminated the study prematurely due to adverse effects. In conclusion, a prostaglandin E₂ analogue, RS-86505-007, has a potent cholesterol-lowering effect, but its grastrointestinal adverse effects are marked. RS-86505-007 could, however, be used as a tool in mechanistic studies of cholesterol metabolism.