caa a22 4500 465812198 CHVBK 20180323112119.0 cr unu---uuuuu 170327e19900101xx s 000 0 eng 10.1007/BF03190129 doi (NATIONALLICENCE)springer-10.1007/BF03190129 Pharmacokinetics of cilazapril during repeated oral dosing in healthy young volunteers [Elektronische Daten] [P. Williams, A. Brown, S. Rajaguru, R. Francis, A. Bell, P. Dewland] Summary: The pharmacokinetics of Cilazapril and its active metabolite cilazaprilat in plasma were investigated in an open study of 13 healthy male volunteers, aged 18 to 43 years. One capsule containing 2.5 mg Cilazapril was administered to each volunteer daily for 8 days. Plasma samples were obtained after the first and eighth doses. Concentrations of Cilazapril, cilazaprilat and activities of angiotensin converting enzyme (ACE) were measured by radioenzymatic methods. For Cilazapril, the values of apparent plasma clearance (about 15 1/h) and volume of distribution (around 28 1) were sufficiently high to suggest that significant pre-systemic hydrolysis to cilazaprilat occurred. There were no significant changes in these values after repeated dosing. There were small, but statistically significant, increases in mean peak concentrations, mean areas under concentration-time curves and mean trough concentrations from the first to the eighth dose. A steady state was achieved after eight doses with an accumulation of 20-30%. The mean effective half-life was approximately 9 h. Despite the accumulation of cilazaprilat in plasma, there were no significant differences in plasma ACE inhibition from the first to the eighth dose. Springer-Verlag, 1990 Cilazapril nationallicence cilazaprilat nationallicence repeated dosing nationallicence accumulation nationallicence Williams P. Pharmacokinetics & Metabolism Department, Roche Products Ltd, Herts AL7 3AY, PO Box 8, Welwyn Garden City, UK aut Brown A. Pharmacokinetics & Metabolism Department, Roche Products Ltd, Herts AL7 3AY, PO Box 8, Welwyn Garden City, UK aut Rajaguru S. Pharmacokinetics & Metabolism Department, Roche Products Ltd, Herts AL7 3AY, PO Box 8, Welwyn Garden City, UK aut Francis R. Pharmacokinetics & Metabolism Department, Roche Products Ltd, Herts AL7 3AY, PO Box 8, Welwyn Garden City, UK aut Bell A. Pharmacokinetics & Metabolism Department, Roche Products Ltd, Herts AL7 3AY, PO Box 8, Welwyn Garden City, UK aut Dewland P. Simbec Research Ltd, Merthyr Tydfil, Mid-Glamorgan, UK aut European Journal of Drug Metabolism and Pharmacokinetics Springer-Verlag 15/1(1990-01-01), 63-67 0378-7966 15:1<63 1990 15 13318 https://doi.org/10.1007/BF03190129 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF03190129 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Williams P. Pharmacokinetics & Metabolism Department, Roche Products Ltd, Herts AL7 3AY, PO Box 8, Welwyn Garden City, UK aut NATIONALLICENCE 700 1- Brown A. Pharmacokinetics & Metabolism Department, Roche Products Ltd, Herts AL7 3AY, PO Box 8, Welwyn Garden City, UK aut NATIONALLICENCE 700 1- Rajaguru S. Pharmacokinetics & Metabolism Department, Roche Products Ltd, Herts AL7 3AY, PO Box 8, Welwyn Garden City, UK aut NATIONALLICENCE 700 1- Francis R. Pharmacokinetics & Metabolism Department, Roche Products Ltd, Herts AL7 3AY, PO Box 8, Welwyn Garden City, UK aut NATIONALLICENCE 700 1- Bell A. Pharmacokinetics & Metabolism Department, Roche Products Ltd, Herts AL7 3AY, PO Box 8, Welwyn Garden City, UK aut NATIONALLICENCE 700 1- Dewland P. Simbec Research Ltd, Merthyr Tydfil, Mid-Glamorgan, UK aut NATIONALLICENCE 773 0- European Journal of Drug Metabolism and Pharmacokinetics Springer-Verlag 15/1(1990-01-01), 63-67 0378-7966 15:1<63 1990 15 13318 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer