Summary
K12.148 (INN: lifibrol), a new cholesterol synthesis inhibitor, was studied in healthy volunteers to evaluate tolerance/safety, the effects on lipids, and pharmacokinetics. In a sequential block design the doses of 150, 300, 600, or 900 mg, given once daily in the morning for 14 consecutive days, were examined in 40 healthy young males (8 active drug and 2 placebo per group, randomized) under well-controlled conditions. Total and LDL cholesterol serum levels decreased significantly in the 300, 600, and 900 mg groups ( -13.4% , - 23.8%, −25.6%, and −14.7%, −33.3%, −34.8% respectively), whereas no significant change was seen with placebo and 150 mg. The antiatherogenic index Apo A-I/B increased in a dose-dependent manner between 300 and 900 mg. Changes in HDL cholesterol and triglycerides were not statistically significant. The study compound was tolerated well, and safety laboratory parameters did not show any relevant alterations. K 12.148 might be a very effective drug for the treatment of hypercholesterolemia.
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References
Kannel WB, Castelli WP, Gordon T, et al. (1971) Serum cholesterol, lipoproteins, and the risk of coronary heart disease: the Framingham study. Ann Intern Med 74: 1–12
The Expert Panel (1988) Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Arch Intern Med 148: 36–69
Illingworth DR (1988) An overview of lipid-lowering drugs. Drugs 36 [Suppl 3]: 63–71
Henwood JM, Heel RC (1988) Lovastatin a preliminary review of its pharmacodynamic properties and therapeutic use in hyperlipidemia. Drugs 36: 429–454
Schliack M, Löser R, Seibel K (1986) Hypolipidemic activity of K 12.148 in rats and marmosets. IXth International Symposium on Drugs Affecting Lipid Metabolism, Florence, 22–25 October 1986
Kulig W Schliack M, Kirchgessner M, et al. (1987) Effect of the hypocholesterolemic compound K 12.148 on the lithogenic index of bile: Reentrant cannula and automatic apparatus for bile study in the pig. International Symposium on Cholesterol Control and Cardiovascular Diseases: Prevention and Therapy, Milan, 7–9 July 1987
Schliack M, Löser R, Seibel K, et al. (1989) Hypolipemic activity of K 12.148 in rats, marmosets and pigs. Artery 16: 90–104
März W, Gross W (1986) Analysis of plasma lipoproteins by ultracentrifugation in a new fixed angle rotor: evaluation of a phosphotungstic acid/MgCl2 precipitation and a quantitative lipoprotein electrophoresis assay. Clin Chim Acta 160: 1–18
Tobert JA, Hitzenberger G, Kukovetz WR, et al. (1982) Rapid and substantial lowering of human serum cholesterol by mevinolin (MK-803), an inhibitor of hydroxymethylglutarylcoenzyme A reductase. Atherosclerosis 41: 61–65
Tobert JA, Bell GD, Birtwell J, et al. (1982) Cholesterol-lowering effect of mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, in healthy volunteers. J Clin Invest 69: 913–919
Nakaya N, Homma Y, Tamachi H, et al. (1986) The effect of CS514, an inhibitor of HMG-CoA reductase, on serum lipids in healthy volunteers. Atherosclerosis 61: 125–128
Pan HY, Willard DA, Waclawski AP, et al. (1987) Clinical pharmacology of pravastatin (SQ 31,000). International Symposium on Cholesterol Control and Cardiovascular Diseases: Prevention and Therapy, Milan, 7–9 July 1987
Illingworth DR (1986) Comparative efficacy of once versus twice daily mevinolin in the therapy of familial hypercholesterolemia. Clin Pharmacol Ther 40: 338–343
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Hasibeder, H., Staab, H.J., Seibel, K. et al. Clinical pharmacology of the hypocholesterolemic agent K 12.148 (lifibrol) in healthy volunteers. Eur J Clin Pharmacol 40, S91–S94 (1991). https://doi.org/10.1007/BF01409417
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DOI: https://doi.org/10.1007/BF01409417