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Effects of single-dose and short-term oral captopril on hepatic blood flow and haemodynamics in mild to moderate hypertensive patients

University of British Columbia

The angiotensin converting enzyme inhibitor, captopril has been extensively used in the treatment of mild to moderate hypertension and congestive heart failure. Although the haemodynamic changes associated with acute and/or chronic captopril therapy have been extensively studied, there is conflicting information of its influence on hepatic blood flow (QH). Most of the human studies have been investigated the influence of captopril on after single-dose administration and very few data are available on its effects after chronic therapy. The most frequently used method to estimate is based on the hepatic clearance of indocyanine green (ICG) from the blood. This thesis reports i) the effects of single-dose (100 mg) and two-weeks (100 mg/day) captopril treatment on QH, assessed by ICG clearance, in six mild to moderate hypertensive male subjects, ii ) the changes in the area under the serum concentration-time curve (AUC) and plasma clearance (ClpICG) of ICG, iii ) the changes in blood pressure, heart rate and splanchnic vascular resistance (SVR) before and after acute and short-term captopril therapy, iv) the effects of postural change from sitting to upright on ClpICG and QH blood pressure, heart rate and SVR before and after two-weeks captopril therapy, v) the effects of acute and two-weeks captopril treatment on some important pharmacokinetic parameters of unchanged captopril. There were two study days two-weeks apart (day 1 and day 14). was estimated at baseline seated, upright, reseated and 1 hour after captopril dosing on the first study day. The same procedures were repeated in the same patients following 14 days captopril therapy. The serum concentration of ICG was determined by spectrophotometric analysis following intravenous ICG dose of 0.45 mg/kg. There was a slight ~ 5% and ~ 6% decrease, but, no significant change in ClpICG and QH, respectively, whether expressed in absolute terms or per unit body weight or body surface area, following the initial and terminal doses of captopril. A significant 25%-29% (p = 0.04) increase in ICG plasma clearance after two-weeks captopril treatment was observed in all of the four study phases (seated, upright, reseated and post-captopril) as compared to control values. Liver blood flow increased substantially, in the four study phases, in the range from 21% to 25% (p = 0.06) after 14 days treatment with captopril. Systolic and diastolic blood pressures were reduced significantly after the initial dose of captopril from 160.5 ± 5.3 and 103.3 ± 1 mm Hg to 132.4 ± 9.3 mm Hg (p < 0.005) and 86.6 ± 6.3 mm Hg (p

Thesis/Dissertation

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2009-01-09

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http://hdl.handle.net/2429/3474

Pharmaceutical Sciences

University of British Columbia

UBCV

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