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Effects of pravastatin on plasma and urinary mevalonate concentrations in subjects with familial hypercholesterolaemia: a comparison of morning and evening administration

  • Pharmacodynamics
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Abstract

In order to determine whether there is a difference in the effect of the hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pravastatin on cholesterol synthesis between the morning and the evening, we studied the 24-h profile of mevalonate in plasma and urine in 11 subjects with heterozygous familial hypercholesterolaemia. In study 1, eight subjects with familial hypercholesterolaemia took pravastatin (20 mg) once in the morning, and another 20-mg dose in the evening after a 1-week wash-out period. In study 2, five subjects with familial hypercholesterolaemia took pravastatin (20 mg per day) in the morning on 3 consecutive days and on 3 days in the evening after a 1 day wash-out. Plasma mevalonate concentrations were reduced at 9 h and 5 h after pravastatin administration in the morning and the evening, respectively. Urinary mevalonate excretion was significantly reduced at 4–8 h after pravastatin administration in the morning (51 vs 19 nmol · h−1) and at 4–16 h after pravastatin administration in the evening (56 vs 27 nmol · h−1). Daily urinary mevalonate excretion was equally and significantly reduced by pravastatin in the morning or evening. In conclusion, we found that morning and evening administration of pravastatin caused equal reductions in plasma and urinary mevalonate concentrations.

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References

  1. Edwards PA, Muroya H, Gould RG (1972) In vivo demonstration of the circadian rhythm of cholesterol synthesis in a liver and intestine of the rat. J Lipid Res 13:396–401

    Google Scholar 

  2. Ho KJ (1979) Circadian rhythm of cholesterol biosynthesis: dietary regulation in the liver and small intestine of hamsters. Int J Chronobiol 6:39–50

    Google Scholar 

  3. Jones PJH, Schoeller DA (1990) Evidence for diurnal periodicity in human cholesterol synthesis. J Lipid Res 31:667–673

    Google Scholar 

  4. Parker TS, McNamara DJ, Brown C, Garrigan O, Kolb R, Batwin H, Ahrens EH Jr (1982) Mevalonic acid in human plasma: relationship of concentration and circadian rhythm to cholesterol synthesis rate in man. Proc Natl Acad Sci USA 79:3037–3041

    Google Scholar 

  5. Popjak G, Boehm G, Parker TS, Edmond J, Edwards PA, Fogelman AM (1979) Determination of mevalonate in blood plasma in man and rat. Mevalonate “tolerance” tests in man. J Lipid Res 20:716–728

    Google Scholar 

  6. Parker TS, McNamara DJ, Brown CD, Kolb R, Ahrens EH Jr (1984) Plasma mevalonate as a measure of cholesterol synthesis in man. J Clin Invest 74:795–804

    Google Scholar 

  7. Kempen HJM, Glatz JFC, Leuven JAG, van der Voor HA, Katan MB (1989) Serum lathosterol concentration is an indicator of whole-body cholesterol synthesis in humans. J Lipid Res 29:1149–1155

    Google Scholar 

  8. Miettinen TA (1982) Diurnal variation of cholesterol precursors squalene and methyl sterols in human plasma lipoproteins. J Lipid Res 23:466–473

    Google Scholar 

  9. Miettinen TA (1985) Cholesterol precursors and their diurnal rhythm in lipoproteins of patients with jejunoileal bypass and ileal dysfunction. Metabolism 34:425–430

    Google Scholar 

  10. Nakamura T, Matsuzawa Y, Takemura K, Kubo M, Miki H, Tarui S (1991) Combined treatment with chenodeoxycholic acid and pravastatin improves plasma cholestanol levels associated with marked regression of tendon xanthomas in cerebrotendinous xanthomatosis. Metabolism 40:741–746

    Google Scholar 

  11. Nozaki S, Kubo M, Sudo H, Matsuzawa Y, Tarui S (1986) The role of hepatic triglyceride lipase in the metabolism of intermediate-density lipoprotein-postheparin lipolytic activities determined by a sensitive, non-radioisotopic method in hyperlipidemic patients and normals. Metabolism 35:53–58

    Google Scholar 

  12. Nakura K, Imada I, Sato K, Sakota K, Kawakami M (1992) An improved assay for mevalonic acid in blood (in Japanese). Igaku to Yakugaku 27:939–945

    Google Scholar 

  13. Jones PJH, Papue AS, Illingworth DR, Leith CA (1992) Correspondence between plasma mevalonic acid levels and deuterium uptake in measuring human cholesterol synthesis. Eur J Clin Invest 22, 609–613

    Google Scholar 

  14. Pappu AS, Illingworth DR, Bacon S (1989) Reduction in plasma low-density lipoprotein cholesterol and urinary mevalonic acids by lovastatin in patients with heterozygous familial hypercholesterolemia. Metabolism 38:542–549

    Google Scholar 

  15. Illingworth DR (1986) Comparative efficacy of once versus twice daily mevinolin in the therapy of familial hypercholesterolemia. Clin Pharmacol Ther 40:338–343

    Google Scholar 

  16. The Lovastatin Study Group I (1990) A multicenter comparison of lovastatin and probucol for treatment of severe primary hypercholesterolemia. Am J Cardiol 66:22B–30B

    Google Scholar 

  17. Nakaya N, Kuta T, Matsuzawa Y, Saito Y, Nakai T, Yamamoto A, Goto Y (1990) Clinical study of pravastatin (CS-514) at once-daily dosage in hyperlipidemia — double-blind comparative study between morning and evening therapy (in Japanese). Rinsyo Iyaku 6:1804–1828

    Google Scholar 

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Nozaki, S., Nakagawa, T., Nakata, A. et al. Effects of pravastatin on plasma and urinary mevalonate concentrations in subjects with familial hypercholesterolaemia: a comparison of morning and evening administration. Eur J Clin Pharmacol 49, 361–364 (1996). https://doi.org/10.1007/BF00203778

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  • DOI: https://doi.org/10.1007/BF00203778

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