Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences

Clinical Pharmacokinetics

Volumn 32, Issue 5, 1997, Pages 403-425

  Lennernäs, Hans ^a   Fager, Gunnar ^b,c  

^a UPPSALA UNIVERSITY   (Sweden)

^b UNIVERSITY OF GOTHENBURG   (Sweden)

^c ASTRAZENECA R AND D   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTEROL; FLUINDOSTATIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MEVINOLIN; PRAVASTATIN; SIMVASTATIN;

AGE; ATHEROSCLEROSIS; BRAIN; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL SYNTHESIS; DISEASE COURSE; DOSE RESPONSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DETERMINATION; DRUG DISTRIBUTION; DRUG METABOLISM; DRUG POTENCY; DRUG TRANSPORT; HUMAN; HYPERCHOLESTEROLEMIA; ISCHEMIC HEART DISEASE; LIVER; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; REVIEW; SEX DIFFERENCE;

EID: 0030953045     PISSN: 03125963     EISSN: None     Source Type: Journal    
DOI: 10.2165/00003088-199732050-00005     Document Type: Review

References (117)

1. Superko HR, Krauss MR. Coronary artery disease regression - convincing evidence for the benefit of aggressive lipoprotein management. Circulation 1994; 90: 1056-69
2. Levine GN, Keaney Jr JF, Vita JA. Cholesterol reduction in cardiovascular disease - clinical benefits and possible mechanisms. N Engl J Med 1995; 332: 512-21
3. Gotto AM. Lipid lowering, regression, and coronary events - a review of the interdisciplinary council on lipids and cardiovascular risk intervention, Seventh Council meeting. Circulation 1995; 92: 647-56
4. Brown BG, Zhao XQ, Sacco DE, et al. Lipid lowering and plaque regression. New insights into prevention of plaque disruption and clinical events in coronary disease. Circulation 1993; 87: 1781-91
5. Holme I. Cholesterol reduction and its impact on coronary artery disease and total mortality. Am J Cardiol 1995; 76: 10C-17C
6. Pedersen TR, Kjekshus J, Berg K, et al. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian simvastatin survival study (4S) Lancet 1994; 344: 1383-9
7. Shepherd J, Cobbe SM, Ford I, et al. for the West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995; 333: 1301-7
8. Sacks FM, Pfeffer MA, Lemeul AM, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996; 335: 1001-9
9. Holme I. An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence. Circulation 1990; 82: 1916-24
10. Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature 1990; 343: 425-30
11. Sirtori CR. Tissue selectivity of hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors. Pharmacol Ther 1993; 60: 431-59
12. Brown MS, Goldslein JL. A receptor-mediated pathway for cholesterol homeostasis. Science 1986; 232: 34-47
13. Endo A, Kuroda M, Tsujita Y. ML-236A, ML-236B and ML-236C. Now inhibitors of cholesterogenesis produced by Penicillium citrinum. J Antibiot 1976; 29: 1346-8
14. Alberts AW, Chen J, Kuron G, et al. Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc Natl Acad Sci USA 1980; 77: 3957-61
15. Hoffman WF, Alberts AW, Anderson PS, et al. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors: 4. Side chain ester derivatives of mevinolin. J Med Chem 1986; 29: 849-52
16. Nakaya N, Homma Y, Tamachi H, et al. The effect of CS-514 on serum lipids and apolipoproteins in hypercholesterolemic subjects. JAMA 1987; 257: 3088-43
17. Plosker GL, Wagstaff AJ. Fluvastatin: a review of its pharmacology and use in the management of hypercholesterolaemia. Drugs 1996; 51: 433-59
18. Dain JG, Fu E, Gorski J, et al. Biotransformation of fluvastatin sodium in humans. Drug Metab Dispos 1993; 21: 567-72
19. Tse FLS, Jaffe JM, Troendle A. Pharmacokinetics of fluvastatin after single and multiple doses in normal volunteers. J Clin Pharmacol 1992; 32: 630-8
20. Tse FLS, Smith HT, Ballard FH, et al. Disposition of fluvastatin, an inhibitor of HMG-CoA reductase, in mouse, rat, dog, and monkey. Biopharm Drug Dispos 1990; 11: 519-31
21. Serajuddin ATM, Ranadive SA, Mahoney EM, et al. Relative lipophilicities, solubilities, and structure-pharmacological considerations of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors pravastatin, lovastatin, mevastatin, and simvastatin. J Pharm Sci 1991; 80: 830-34
22. Garnett WR. The pharmacology of fluvastatin, a new HMG-CoA reductase inhibitor. Clin Cardiol 1994; 17 Suppl. IV IV-3-1V-10
23. Cilla Jr DD, Whitfield LR, Gibson DM, et al. Multiple-dose pharmacokinetics, pharmacodynamics and safety of atorvastatin, an inhibitor of HMG-CoA reductase, in healthy subjects. Clin Pharmacol Ther 1996; 60 (6): 687-695
24. Mitchel YB. The long-term tolerability profile of lovastatin and simvastatin. Atherosclerosis 1992; 97: S33-S39
25. Illingworth DR, Tobert JA. A review of clinical trials comparing HMG-CoA reductase inhibitors. Clin Ther 1994; 16: 366-85
26. Fager G. The clinical documentation of fluvastatin. Astra Hässle AB, 1995
27. Jacotot B, Benghozi R, Pfister P, et al. Comparison of fluvastatin versus pravastatin treatment of primary hypercholesterolemia. Am J Cardiol 1995; 76: 54A-56A
28. Haasis R, Berger J. Fluvastatin versus lovastatin - eine randomisierte, doppelblinde, multizentrische parallel gruppen studie zur effektivität und sicherheit einer lipdsenkung. Herz Kreislauf 1995; 27: 375-80
29. Schulte K-L, Beil S. Efficacy and tolerability of fluvastatin and simvastatin in hypercholesterolaemic patients: a double-blind, randomised, parallel-group comparison. Clin Drug Invest 1996; 12: 119-26
30. Ose L, Scott R. Simvastatin-Fluvastatin Study Group. Double-blind comparison of the efficacy and tolerability of simvastatin and fluvastatin in patients with primary hypercholesterolaemia. Clin Drug Invest 1995; 10: 127-38
31. Illingworth DR, Sten EA, Knopp RH, et al. A randomized multicenter trial comparing the efficacy of simvastatin and fluvastatin. J Cardiovasc Pharmacol Ther 1996; 1: 23-30
32. Desplypere JP. Simvastatin-fluvastatin comparative study. Clin Drug Invest 1996; 11: 362-63
33. Deslypere JP. Simvastatin-fluvastatin comparative study - contined [letter]. Clin Drug Invest 1996; 12: 57
34. Haasis R, Berger J, Andersson F, et al. A pharmacoeconomic evaluation of fluvastatin and lovastatin in primary hypercholesterolaemia. Br J Med Econ 1996; 10: 145-57
35. Herd JA, Ballantyne CM, Farmer JA. The effect of fluvastatin on coronary atherosclerosis: the Lipoprotein and Coronary Atherosclerosis Study (LCAS). Circulation 1996; 94 Suppl.: abstract 3496
36. Barr WH. The role of intestinal metabolism on bioavailability. In: Welling PG, Tse FLS, Dighe SV, editors. Pharmaceutical bioequivalence. New York: Marcel Dekker, 1991: 149-68
37. De Waziers I, Cugnenc PH, Yang CS, et al. Cytochrome P450 isoenzymes, epoxide hydrolase and glulathione transferase in rat and human hepatic and extrahepatic tissues. J Pharmacol Exp Ther 1990; 253: 387-94
38. Kyvöstö KT, Boojkans G, Fromm MF, et al. Expression of CYP 3A4, CYP 3A5 and CYP 3A7 in human duodenal tissue. Br J Clin Pharmacol 1996; 42: 387-9
39. Thummel KE, Diarmuid O'S, Paine MF, et al. Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism. Clin Pharmacol Ther 1995; 59: 491-502
40. Lindahl A, Sandström R, Ungell A-L, et al. Jejunal permeability and hepatic extraction of fluvastatin in humans. Clin Pharmacol Ther 1996; 60: 493-503
41. Tse FLS, Labbadia D. Absorption and disposition of fluvastatin, an inhibitor of HMG-CoA reductase, in the rabbit. Biopharm Drug Dispos 1992; 13: 285-94
42. 3H]fluvastatin following single oral doses in beagle dogs and rhesus monkeys with bile fistulae. Biopharm Drug Dispos 1995; 16: 211-9
43. Transon C, Leemann T, Dayer P, et al. Selective in vitro inhibition profile by fluvastatin indicates its potential in vivo drug interactions. Clin Pharmacol Ther 1993; abstract P11-74
44. Transon C, Leemann T, Dayer P. In vitro comparative inhibition profiles of major drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors. Eur J Clin Pharmacol 1996; 50: 209-15
45. Smith HT, Jokubaitis LA, Troendle AJ, et al. Pharmacokinetics of fluvastatin and specific drug interactions. Am J Hypertens 1993; 6: 17-26
46. Lennernäs H, Ahrenstedt Ö, Hällgren R, et al. Regional jejunal perfusion, a new in vivo approach to study oral drug absorption in man. Pharm Res 1992; 9: 1243-51
47. Duggan DE, Chen I-W, Bayne WF, et al. The physiological disposition of lovastatin. Drug Metab Dispos 1988; 17: 166-73
48. Wils P, Warnery A, Phung-Ba V, et al. High lipophilicity decreases drug transport across intestinal epithelial cells. J Pharmacol Exp Ther 1994; 269: 1268-77
49. Dimitroulakos J, Yeger H. HMG-CoA reductase mediates the biological effects of retinoic acid on human neuroblastoma cells: lovastatin specifically targets P-glycoprotein expressing cells. Nature Med 1996; 2: 326-33
50. Schinkel AH, Smit JJM, Tellingen van O, et al. Disruption of the mouse mdr 1a P-glycoprotein gene leads to deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994; 77: 491-502
51. Leveille-Webster CR, Arias IM. The biology of the P-glycoproteins. J Membr Biol 1995; 143: 89-102
52. Pan HY, DeVault AR, Wang-Iverson D, et al. Comparative pharmacokinetics and pharmacodynamics of pravastatin and lovastatin. J Clin Pharmacol 1990; 30: 1128-35
53. Pan HY. Clinical pharmacology of pravastatin, a selective inhibitor of HMG-CoA reductase. Eur J Pharmacol 1991; 40 Suppl. 1: S8-S15
54. Quion JAV, Jones PH. Clinical pharmacokinetics of pravastatin. Clin Pharmacokinet 1994; 27: 94-103
55. Singhvi SM, Pan HY, Morrison RA, et al. Disposition of pravastatin sodium, a tissue-selective HMG-CoA reductase inhibitor, in healthy subjects. Br J Clin Pharmacol 1990; 29: 239-43
56. Palm K, Luthman K, Ungell A-L, et al. Correlation of drug absorption with molecular surface properties. J Pharm Sci 1996; 85: 32-9
57. Van de Waterbeemd H, Camenisch G, Folkers G, et al. Physicochemical models of Caco-2 transport by passive diffusion. Quant Struct Act Relat. In press
58. Triscari J, O'Donnell D, Zinny M, et al. Gastrointestinal absorption of pravastatin in healthy subjects. J Clin Pharmacol 1995; 35: 142-4
59. Vickers S, Duncan CA, Chen I-W, et al. Metabolic disposition studies on simvastatin, a cholesterol-lowering prodrug. Drug Metab Dispos 1989; 18: 138-45
60. Cheng H, Sutton SC, Pipkin JD, et al. Evaluation of sustained/controlled-release dosage forms of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors in dogs and humans. Pharm Res 1993; 10: 1683-7
61. Tang B-K, Kalow W. Variable activation of lovastatin by hydrolytic enzymes in human plasma and liver. Eur J Clin Pharmacol 1995; 47: 449-51
62. Rowland M, Tozer T. Clinical pharmacokinetics. 2nd ed. Philadelphia (PA): Lea & Febiger, 1989
63. Tse FLS, Nickerson DF, Yardley WS. Binding of fluvastatin to blood cells and plasma proteins. J Pharm Sci 1993; 82: 942-7
64. Koga T, Fukuda K, Shimada Y, et al. Lovastatin and simvastatin: the relationship between inhibition of de novo sterol synthesis and active drug concentrations in the liver, spleen, and testis in rat. Eur J Biochem 1992; 209: 315-9
65. Rolan PE. Plasma protein binding displacement interactions - why are they still regarded as clinically important? Br J Clin Pharmacol 1994; 37: 125-28
66. Goldslein JL, Brown MS. Regulation of the mevalonate pathway. Nature 1990; 343; 425-30
67. Transon C, Leemann T, Vogt N, et al. In vivo inhibition profile of cytochrome P450tb (CYP2C9) by (±)-fluvastatin. Clin Pharmacol Ther 1995; 58: 412-7
68. Lennernäs H, Regårdh CG. Dose-dependent intestinal absorption and significant intestinal excretion (exsorption) of the β-blocker pafenolol in the rat. Pharm Res 1993; 10: 727-31
69. Wetterich U, Spahn-Langguth H, Mutschler E, et al. Evidence for intestinal secretion as an additional clearance pathway of talinolol enantiomers: concentration- and dose-dependent absorption in vitro and in vivo. Pharm Res 1996; 13: 514-22
70. Everett DW, Chando TJ, Didonato GC, et al. Biotransformation of pravastatin sodium in humans. Drug Metab Dispos 1991; 19: 740-8
71. Kitazawa E, Tamura N, Iwabuchi H, et al. Biotransformation of pravastatin sodium. I. Mechanisms of enzymic transformation and epimerization of an allylic hydroxy group of pravastatin sodium. Biochem Biophys Res Commun 1993; 142: 597-602
72. Duggan DE, Vickers S. Physiological disposition of HMG-CoA-reduclase inhibitors. Drug Metab Rev 1990; 22: 333-62
73. Mauro VF. Clinical pharmacokinetics and practical applications of simvastatin. Clin Pharmacokinet 1993; 24: 195-202
74. Wang RW, Karl PH, Lu AYH, et al. Biotransformation of lovastatin. IV. Identification of cytochrome P450 3A proteins as the major enzymes responsible for the oxidative metabolism of lovastatin in rat and human liver microsomes. Arch Biochem Biophys 1991; 290: 355-61
75. Cheng H, Rogers JD, Sweany AE, et al. Influence of age and gender on the plasma profiles of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitory activity following multiple doses of lovastatin and simvastatin. Pharm Res 1992; 9: 1629-34
76. Vyas KP, Kari PH, Pitzenberger SM. Regioselectivity and stereoselectivity in the metabolism of HMG-CoA reductase inhibitors. Biochem Biophys Res Commun 1990; 166: 1155-62
77. Simvastatin manufacturing information. US: Merck & Co. Inc., 1991
78. Mckenney JM. Lovastatin: a new cholesterol-lowering agent. Clin Pharm 1988; 7: 21-38
79. Holtzman JL, Finley DK, Zhou LX, et al. Interaction between isradipine and lovastatin in normal male volunteers. Clin Pharmacol Ther 1993; abstract P1-116
80. Stein WD. Transport and diffusion across cell membranes. New York: Academic Press, 1986
81. Germershausen JI, Hunt VM, Bostedor RG, et al. Tissue selectivity of the cholesterol-lowering agents lovastatin, simvastatin and pravastatin in rats in vivo. Biochem Biophys Res Commun 1989; 158: 667-75
82. Komai T, Shigehara E, Tokui T, et al. Carrier-mediated uptake of pravastatin by rat hepatocytes in primary culture. Biochem Pharmacol 1992; 43: 667-70
83. Sathirakul K, Suzuki H, Yamada T, et al. Multiple transport systems for organic anions across the bile canalicular membrane. J Pharmacol Exp Ther 1993; 268: 65-72
84. Shaw MK, Newton RS, Sliskovic DR. Hep-G2 cells and primary rat hepatocytes differ in their response to inhibitors of HMd-CoA reductase. Biochem Biophys Res Commun 1990; 170: 726-34
85. +-independent multispecific anion transporter mediates active transport of pravastatin into rat liver. Am J Physiol 1993; 264: G36-44
86. Ziegler K, Hummelsiep S. Hepatoselective carrier-mediated sodium-independent uptake of pravastatin and pravastatin-lactone. Biochim Biophys Acta 1993; 1153: 23-33
87. Yamazaki M, Akiyama S, Nishigaki R, et al. Uptake is the rate-limiting step in the overall hepatic elimination of pravastatin at steady-state in rats. Pharm Res 1996; 13: 1559-64
88. Guillot F, Misslin P, Lemaire M. Comparison of fluvastatin and lovastatin blood-brain barrier transfer using in vitro and in vivo methods. Pharm Res 1993; 21: 339-46
89. Saheki A, Terasaki T, Tamai I, et al. In vivo and in vitro blood-brain barrier transport of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Pharm Res 1994; 11: 305-11
90. Tsuji A, Saheki A, Tamai I, et al. Transport mechanism of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors at the blood-brain barrier. J Pharmacol Exp Ther 1993; 267: 1085-90
91. Eckernäs S-A, Roos B-E, Kvidal P, et al. The effects of simvastatin and pravastatin on objective and subjective measures of nocturnal sleep: a comparison of two structurally different HMG CoA reductase inhibitors in patients with primary moderate hypercholesterolaemia. Br J Clin Pharmacol 1993; 35: 284-9
92. Harrison RWS, Ashton CH. Do cholesterol-lowering agents affect brain activity? A comparison of simvastatin, pravastatin, and placebo in healthy volunteers. Br J Clin Pharmacol 1994; 37: 231-6
93. Pan HY, Waclawski AP, Funke PT, et al. Pharmacokinetics of pravastatin in elderly versus young men and women. Ann Pharmacother 1993; 27: 1029-33
94. Smit JWA, Wijne HJA, Schobben F, et al. Effects of alcohol consumption on pharmacokinetics, efficacy, and safety of fluvastatin. Am J Cardiol 1995; 76: 89A-96A
95. Pan HY, DeVault AR, Brescia D, et al. Effect of food on pravastatin pharmacokinetics and pharmacodynamics. Int J Clin Pharmacol Ther Toxicol 1993; 31: 291-4
96. Garnett WR. Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors. Am J Health Syst Pharm 1995; 52: 1639-45
97. Ritcher WO, Jacob BG, Schwandt P. Interaction between fibre and lovastatin [letter]. Lancet 1991; 338: 706
98. Triscari J, Rossi L, Pan HY. Chronokinetics of pravastatin administered in the pm compared with am dosing. Am J Ther 1995; 2: 265-8
99. Appel S, Rüfenacht T, Kalafsky G, et al. Lack of interaction between fluvastatin and oral hypoglycemic agents in healthy subjects and in patients with non-insulin-dependent diabetes mellitus. Am J Cardiol 1995; 76: 29A-32A
100. Spence JD, Munoz CE, Hendricks L, et al. Pharmacokinetics of the combination of fluvastatin and gemfibrozil. Am J Cardiol 1995; 76: 80A-3A
101. Goldberg R, Roth D. Fluvastatin safety, efficacy and kinetics in the treatment of hypercholesterolemia in renal-transplant patients receiving cyclosporine. Proceedings of the 10th International Symposium on Atherosclerosis; 1994 Oct 9-14; Montreal: 6a-d
102. Jokubaitis LA. Updated clinical safety experience with fluvastalin. Am J Cardiol 1994; 73: 18D-24D
103. Plosker GL, Wagstaff AJ. Fluvastatin: a review of its pharmacology and use in the management of hypercholesterolaemia. Drugs 1996; 51: 433-59
104. Cheng H, Rogers JD, Sweany AE, et al. Influence of age and gender on the plasma profiles of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitory activity following multiple doses of lovastatin and simvastatin. Pharm Res 1992; 9: 1629-34
105. Pan HY, Triscari J, DeVault AR, et al. Pharmacokinetic interaction between propranolol and the HMG-CoA reductase inhibitors pravastatin and lovastatin. Br J Clin Pharmacol 1991; 31: 665-70
106. Tobert JA. Efficacy and long-term adverse effect pattern of lovastatin. Am J Cardiol 1988; 62: 28J-34J
107. Corpier CL, Jones PH, Wadi NS, et al. Rhabdomyolysis and renal injury with lovastatin use. The report of two cases in cardiac transplant recipients. JAMA 1988; 260: 239-41
108. Illingworth DR, Bacon SP, Larsen KK. Long-term experience with HMG-CoA reductase inhibitors in the therapy of hypercholesterolemia. Atherosclerosis Rev 1988; 18: 46-7
109. Pierce LR, Wysowski DK, Grogs TP. Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy. JAMA 1990; 264: 71-5
110. Ahmad S. Lovastatin: warfarin interaction. Arch Intern Med 1990; 150: 2407
111. Hoffman HS. The interaction of lovastatin and warfarin. Conn Med 1992; 56: 107
112. Pan HY, DeVault AR, Swites BJ, et al. Pharmacokinetics and pharmacodynamics of pravastatin alone and with cholestyramine in hypercholesterolemia. Clin Pharmacol Ther 1990; 48: 201-7
113. Regazzi MB, Iacona I, Campana C, et al. Clinical efficacy and pharmacokinetics of HMG-CoA reductase inhibitors in heart transplant patients treated with cyclosporin A. Transplant Proc 1994; 26: 2644-5
114. Meyer BH, Scholtz HE, Müller FO, et al. Lack of interaction between ramipril and simvastatin. Eur J Clin Pharmacol 1994; 47: 373-5
115. Triscari J, Swanson BN, Willard DA, et al. Steady state serum concentrations of pravastatin and digoxin when given in combination. Br J Clin Pharmacol 1993; 36: 263-5
116. Campana C, Iacona I, Regazzi MB, et al. Efficacy and pharmacokinetics of simvastatin in heart transplant recipients. Ann Pharmacother 1995; 29: 235-9
117. Smith PF, Eydelloth RS, Grossman SJ, et al. HMG-CoA reductase inhibitor-induced myopathy in the rat: cyclosporin A interaction and mechanism studies. J Pharmacol Ther 1991; 257: 1225-35