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Desirable Lipoprotein Parameters in Early Drug Trials

  • C. R. Sirtori
  • A. Bondioli
Conference paper
Part of the Proceedings in Life Sciences book series (LIFE SCIENCES)

Abstract

Lipid-lowering drugs may be tested very early in patients, in view of the overall “normality” of these subjects, aside from their specific biochemical disorder. Although current modalities for the early evaluation of new drug products require administration to “healthy” volunteers, it is becoming more and more common to carry out early testing in “healthy” subjects with elevated plasma lipid levels. In view of the high expectation for new drug products, active in primary hyperlipoproteinemias (The Lipid Research Clinics 1984), we personally consider as feasible and advisable to carry out the Phase I evaluation of new drugs for hyperlipidemia in patients. These should possibly never have received drug treatments or, in some cases, should be evaluated after stopping treatment with specific products (e.g. anion-binding resins).

Keywords

High Density Lipoprotein Lipid Research Clinic High Density Lipoprotein Cholesterol Hypertriglyceridemic Patient High Density Lipoprotein Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Avogaro P, Bittolo Bon G, Cazzolato G, Quinci GB (1979) Are apolipoproteins better discriminators than lipids for atherosclerosis? Lancet i:901–903CrossRefGoogle Scholar
  2. Baggio G, Briani G, Fellin R, et al. (1979) Effect of tiadenol on the concentration and composition of serum lipoproteins in familial hypercholesterolemia. Artery 5:486–498Google Scholar
  3. Bengtsson G, Olivecrona T (1980) Lipoprotein lipase: some effects of activator proteins. Eur J Biochem 106:549–555PubMedCrossRefGoogle Scholar
  4. Carlson LA, Kolmodin-Hedman B (1977) Hyper-α-lipo-proteinemia in men exposed to chlorinated hydrocarbon pesticides. Acta Med Scand 201:375–376PubMedCrossRefGoogle Scholar
  5. Deckelbaum RJ, Granot E, Oschry Y, et al. (1984) Plasma triglyceride determines structure-composition in low and high density lipoproteins. Arteriosclerosis 4:225–231PubMedCrossRefGoogle Scholar
  6. Eisenberg S (1985) High density lipoprotein metabolism. J Lipid Res 25:1017–1058Google Scholar
  7. Franceschini G, Poli A, Catapano A, et al. (1981) Pharmacological studies on tiadenol in type IV patients — evidence for a mechanism of action different from other lipid lowering drugs. Atherosclerosis 40:245–255PubMedCrossRefGoogle Scholar
  8. Franceschini G, Bondioli A, Mantero M, et al. (1982) Increased apoprotein B in very low density lipoproteins of patients with peripheral vascular disease. Arteriosclerosis 2:74–80PubMedCrossRefGoogle Scholar
  9. Franceschini G, Sirtori M, Gianfranceschi G, et al. (1985) Reversible increase of the apo CII/CIII-1 ratio in the very low density lipoproteins after procetofen treatment in hypertriglyceridemic patients. Artery 12:363–381PubMedGoogle Scholar
  10. Gaddi A, Descovich GC, Noseda S, et al. (1984) Controlled evaluation of pantethine, a natural hypolipidemic compound in patients with different forms of hyperlipoproteinemia. Atherosclerosis 50:73–83PubMedCrossRefGoogle Scholar
  11. Gibson JC, Rubinstein A, Brown WV (1984) Precipitation of apo E-containing lipoprotein by precipitation reagents for apolipoprotein B. Clin Chem 30:1784–1788PubMedGoogle Scholar
  12. Gidez LI, Miller GJ, Burstein M, Eder HA (1979) Analysis of plasma HDL subclasses by a precipitation procedure. In: Rep HDL Methodology Worksh, NIH Publ 82–1661, Bethesda, MD, p 328Google Scholar
  13. Gugler R (1978) Clinical pharmacokinetics of hypolipidemic drugs. Clin Pharmacokinet 3:425–439PubMedCrossRefGoogle Scholar
  14. Kane JP, Sata T, Hamilton RL, et al. (1975) Apoprotein composition of very low density lipoproteins of human serum. J Clin Invest 56:1622–1634PubMedCrossRefGoogle Scholar
  15. Knopp RH, Ginsberg J, Albert JJ, et al. (1985) Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin. Metabolism 34:642–650PubMedCrossRefGoogle Scholar
  16. Kritchevsky D, Tepper SA, Czarnecky SK, Story JA (1979) Influence of tiadenol, bis (hydroxyethylthio) 1.10 decane, on cholesterol metabolism in rats. Pharmacol Res Commun 11:475–482PubMedCrossRefGoogle Scholar
  17. The Lipid Research Clinics Coronary Primary Prevention Trial Results (1984) J Am Med Assoc 251:351–374CrossRefGoogle Scholar
  18. Mahley RW (1983 Apolipoprotein E and cholesterol metabolism. Klin Wochenschr 61:225–232PubMedCrossRefGoogle Scholar
  19. Mattson FM, Grundy SM (1985) Comparison of effects of dietary saturated, monounsaturated and polyunsaturated fatty acids on plasma lipids and lipoproteins in man. J Lipid Res 26:199–202Google Scholar
  20. Nikkilä EA, Huttunen JK, Ehnholm C (1977) Effect of Clofibrate on post-heparin plasma triglyceride lipase activities in patients with hypertriglyceridemia. Metabolism 26:179–186PubMedCrossRefGoogle Scholar
  21. Pan HY, Willard DA, Funker PT, McKinstry DN (1986) The clinical pharmacology of SQ 31,000 (CS-514) in healthy subjects. IX Int Symp Drugs Affecting Lipid Metabolism. Florence, Italy, October 22–25Google Scholar
  22. Saku K, Gartside PS, Hynd A, Kashyap ML (1986) Mechanism of action of gemfibrozil on lipoprotein metabolism. J Clin Invest 75:1702–1712CrossRefGoogle Scholar
  23. Schmidt SB, Wasserman AG, Muesing RA, et al. (1985) Lipoprotein and apolipoprotein levels in angiographically defined coronary atherosclerosis. Am J Cardiol 55:1459–1462PubMedCrossRefGoogle Scholar
  24. Schmitz G, Assmann G (1982) Isolation of human serum HDLj by zonal ultracentrifugation. J Lipid Res 23:903–910PubMedGoogle Scholar
  25. Schonfeld G, George PK, Miller J, Reilly P, Witztum J (1979) Apolipoprotein C-II and C-III levels in hyperlipoproteinemia. Metabolism 28:1001–1010PubMedCrossRefGoogle Scholar
  26. Simpson HS, Ballantyne FC, Packard CJ, Morgan HG, Shepherd J (1982) High-density lipoprotein subfractions as measured by differential polyanionic precipitation and rate zonal ultracentrifugation. Clin Chem 28:2040–2043PubMedGoogle Scholar
  27. Sirtori CR, Franceschini G (1984) Drug effects on HDL. In: Miller NE, Miller GJ (eds) Clinical and metabolic aspects of high-density lipoproteins. Elsevier, Amsterdam, p 341Google Scholar
  28. Sirtori CR, Montanari G, Gianfranceschi G, et al. (1985) Correlation between plasma levels of fenofibrate and lipoprotein changes in hyperlipidaemic patients. Eur J Clin Pharmacol 28:619–629PubMedCrossRefGoogle Scholar
  29. Sirtori CR, Tremoli E, Gatti E, et al. (1986) Controlled evaluation of fat intake in the Mediterranean diet: comparative activities of olive oil and corn oil on plasma lipids and platelets in high-risk patients. Am J Clin Nutrit 44:635–642PubMedGoogle Scholar
  30. Sirtori CR, Franceschini G, Gianfranceschi G, et al. (1987) Effects of gemfibrozil on plasma lipoprotein/apolipoprotein distribution and platelet reactivity in hypertriglyceridemic patients. J Lab din Med (in press)Google Scholar
  31. Sniderman A, Shapiro S, Marpole D, et al. (1980) Association of coronary atherosclerosis with hyperapobetalipoproteinemia (increased protein but normal cholesterol levels in human plasma low density (β) lipoproteins) Proc Natl Acat Sci USA 77:604–608CrossRefGoogle Scholar
  32. Wallenstein S, Fischer AC (1977) The analysis of the two-period repeated measurements cross-over design with application to clinical trials. Biometrics 33:261–272PubMedCrossRefGoogle Scholar
  33. Warnick GR, Albers JJ (1978) A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating high density lipoprotein cholesterol. J Lipid Res 19:65–76PubMedGoogle Scholar
  34. Warnick GR, Cheung MC, Albers JJ (1979) Comparison of current methods for high-density lipoprotein cholesterol quantitation. Clin Chem 25:596–604PubMedGoogle Scholar
  35. Warnick GR, Albers JJ, Leary ET (1980) HDL cholesterol: results of interlaboratory proficiency test. Clin Chem 26:169–170PubMedGoogle Scholar
  36. Warnick GR, Benderson JM, Albers JJ (1983) Interlaboratory proficiency survey of high-density lipoprotein cholesterol measurement. Clin Chem 29:516–519PubMedGoogle Scholar
  37. Witztum JL, Dillingham MA, Giese W, et al. (1980) Normalization of triglycerides in type IV hyperlipoproteinemia fails to correct low levels of high-density-lipoprotein cholesterol. N Engl J Med 30:907–914CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • C. R. Sirtori
  • A. Bondioli
    • 1
    • 2
  1. 1.Center E. Grossi Paoletti, Institute of Pharmacological SciencesUniversity of MilanoMilanoItaly
  2. 2.Divisione Medica VerganiOspedale di Niguarda Ca’ GrandaMilanoItaly

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