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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

  • Pharmacodynamics
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Abstract

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 μg t.i.d. and a separate group of 26 patients 6 μg 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 μg 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 ε4 allele of the apolipoprotein E than in those with ε3 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 μg t.i.d. and 81% receiving 6 μg t.i.d. had adverse events, two-thirds of which related to the gastrointestinal tract. One patient in the 3-μg group and three patients in the 6-μg 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.

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Authors and Affiliations

  1. Department of Internal Medicine and Biocenter Oulu, University of Oulu, FIN-90220, Kajaanintie 50, Finland

    T. Korhonen, M. J. Savolainen & Y. A. Kesäniemi

  2. Länsi Pohja Central Hospital, Kemi, Finland

    T. Jääskeläinen

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  1. T. Korhonen
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  2. M. J. Savolainen
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  3. Y. A. Kesäniemi
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  4. T. Jääskeläinen
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Korhonen, T., Savolainen, M.J., Kesäniemi, Y.A. et al. 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. Eur J Clin Pharmacol 48, 97–102 (1995). https://doi.org/10.1007/BF00192732

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  • DOI: https://doi.org/10.1007/BF00192732

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