Abstract
Seven sustained/controlled-release dosage forms were designed for gastrointestinal delivery of lovastatin or simvastatin, two potent HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia. The in vivo performance of these formulations was evaluated in dogs and healthy volunteers in terms of the cholesterol lowering efficacy and/or systemic concentrations of HMG-CoA reductase inhibitors. Results from the present and previous studies suggest that, through the controlled release of HMG-CoA reductase inhibitors, sustained lower plasma concentrations of HMG-CoA reductase inhibitors may result in an equal or better therapeutic efficacy.
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REFERENCES
A. Alberts, J. Chen, G. Kuron, V. Hunt, J. Huff, C. Hoffman, J. Rothrock, M. Lopez, H. Joshua, E. Harris, A. Patchett, R. Monaghan, S. Currie, E. Stapley, G. Albers-Schonberg, O. Hensens, J. Hirshfield, K. Hoogsteen, J. Liesch, and J. Springer. Mevinolin. A highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol lowering agent. Proc. Natl. Acad. Sci. 77:3957–3961 (1980).
W. F. Hoffman, A. W. Alberts, P. S. Anderson, J. S. Chen, R. L. Smith, and A. K. Willard. 3-Hydroxy-3-methylglutarylcoenzyme A reductase inhibitors. 4. Side chain ester derivatives of mevinolin. J. Med. Chem. 29:849–852 (1986).
R. H. Bradford, C. L. Shear, A. N. Chremos, C. Dujovne, M. Downton, F. A. Franklin, A. L. Gould, M. Hesney, J. Higgins, D. P. Hurley, A. Langendorfer, D. T. Nash, J. L. Pool, and H. Schnaper. Extended clinical evaluation of lovastatin (EXCEL) study results. Arch. Intern. Med. 151:43–49 (1991).
G. A. McClelland, R. J. Stubbs, J. A. Fix, S. A. Pogany, and G. M. Zentner. Enhancement of 3-hydroxyglutaryl-coenzyme A reductase inhibitor efficacy through administration of a controlled-porosity osmotic pump dosage form. Pharm. Res. 8:873–876 (1991).
D. E. Duggan, I.-W. Chen, W. F. Bayne, R. A. Halpin, C. A. Duncan, M. S. Schwartz, R. J. Stubbs, and S. Vickers. The physiological disposition of lovastatin. Drug Metab. Disp. 17:166–173 (1989).
S. Vickers, C. Duncan, I. Chen, A. Rosegay, and D. Duggan. Metabolic disposition studies on simvastatin, a cholesterol lowering prodrug. Drug Metab. Disp. 18:138–145 (1990).
K. V. R. Rao and K. P. Devi. Swelling controlled-release systems: Recent developments and applications. Int. J. Pharm. 48:1–13 (1988).
G. M. Zentner, G. S. Rork, and K. J. Himmelstein. The controlled porosity osmotic pump. J. Control. Rel. 1:269–282 (1985).
R. J. Stubbs, M. S. Schwartz, R. J. Gerson, T. J. Thornton, and W. F. Bayne. Comparison of plasma profiles of lovastatin, simvastatin, and pravastatin in the dog. Drug Invest. 2(Suppl. 2):18–28 (1990).
C. Allain, L. Poon, C. Chan, W. Richmond, and P. Fu. Enzymatic determination of total serum cholesterol. Clin. Chem. 20:470–475 (1974).
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Cheng, H., Sutton, S.C., Pipkin, J.D. 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 10, 1683–1687 (1993). https://doi.org/10.1023/A:1018997308946
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DOI: https://doi.org/10.1023/A:1018997308946