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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2011.1
- 수록면
- 248 - 254 (7page)
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초록· 키워드
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Biotransformation of pharmacologically inactive lactone prodrug simvastatin (SV) into pharmacologically active simvastatin ${\beta}$-hydroxy acid (SVA) exhibits inter-species differences due to variations in amount and activity of esterase enzymes. In this study, we investigated the pharmacokinetics (PK) of SV and its metabolite SVA following oral doses of SV from controlled-release (CR) tablets and immediate-release (IR) tablets in rodent and canine animal models that features different esterase activity. In rat PK study, no SV was detected in plasma for both formulations due to rapid hydrolysis of SV into SVA by plasma esterase. Besides, no significant differences in PK parameters of SV or SVA were observed between both species. In dog PK study, the relative oral bioavailability of CR tablets in terms of SV was 72.3% compared to IR tablets. Regarding formulation differences in dogs, CR tablets exhibited significantly lower $C_{max}$ (p<0.05), and higher $T_{max}$ (p<0.01) and MRT (p<0.01) for both SV and SVA compared to IR tablets. Accordingly, CR tablets of SV with prolonged drug release profiles in both species might be a potential candidate for a more effective delivery of SV with reduced side effects. Besides, similar PK parameters of SV and SVA in both species despite variation in enzyme activities suggested involvement of equally potent biotransformation pathways in these animal species.
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참고문헌 (36)
참고문헌 신청
Alberts, A. W / 1988 / Discovery, biochemistry and biology of lovastatin. / Am. J. Cardiol 62:10~15
Alberts, A. W / 1990 / Effects of HMG CoA reductase inhibitors on cholesterol synthesis / Drug Invest 2:9~17
Alberts, A. W / 1980 / Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterollowering agent / Proc. Natl. Acad. Sci. U.S.A 77:3957~9361
Black, A. E / 1999 / Metabolism and excretion of atorvastatin in rats and dogs / Drug Metab. Dispos 27:916~923
Bradford, R. H / 1991 / Expanded clinical evaluation of lovastatin (EXCEL) study results: I. Effi cacy in modifying plasma lipoproteins and adverse event profi le in 8245 patients with moderate hypercholesterolemia / Arch. Intern. Med 151:43~49
Alberts, A. W / 1990 / Effects of HMG CoA reductase inhibitors on cholesterol synthesis / Drug Invest 2:9~17
Alberts, A. W / 1980 / Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterollowering agent / Proc. Natl. Acad. Sci. U.S.A 77:3957~9361
Black, A. E / 1999 / Metabolism and excretion of atorvastatin in rats and dogs / Drug Metab. Dispos 27:916~923
Bradford, R. H / 1991 / Expanded clinical evaluation of lovastatin (EXCEL) study results: I. Effi cacy in modifying plasma lipoproteins and adverse event profi le in 8245 patients with moderate hypercholesterolemia / Arch. Intern. Med 151:43~49
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