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 micrograms t.i.d. and a separate group of 26 patients 6 micrograms 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 micrograms 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 epsilon 4 allele of the apolipoprotein E than in those with epsilon 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 percent of patients receiving 3 micrograms t.i.d. and 81% receiving 6 micrograms t.i.d. had adverse events, two-thirds of which related to the gastrointestinal tract. One patient in the 3-micrograms group and three patients in the 6-micrograms group terminated the study prematurely due to adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Korhonen
T
T
Department of Internal Medicine, University of Oulu, Finland.
Savolainen
M J
MJ
Jääskeläinen
T
T
Kesäniemi
Y A
YA
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D016620:Enprostil / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D013997:Time Factors
D000924:Anticholesteremic Agents; D008055:Lipids; D008074:Lipoproteins; D010919:Placebos; D002784:Cholesterol; D016620:Enprostil