Pharmacokinetic Optimisation of Angiotensin Converting Enzyme (ACE) Inhibitor Therapy

Burnier, Michel; Biollaz, J.

doi:10.2165/00003088-199222050-00004

Cited by 24 publications

(14 citation statements)

References 39 publications

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“…Most of the ACE inhibitors are excreted through the kidney by glomerular filtration and tubular secretion. In the presence of renal impairment their plasma concentration increases [103,104]. Therefore, the dose needs to be adjusted accordingly, especially when the creatinine clearance is below 30 ml min -1 [103,104].…”

Section: Ace Inhibitorsmentioning

confidence: 99%

“…Therefore, the dose needs to be adjusted accordingly, especially when the creatinine clearance is below 30 ml min -1 [103,104]. Some of the newer ACE inhibitors, such as benazepril, fosinopril, spirapril, and zofenopril, are also eliminated by the biliary route thus potentially compensating for the reduced renal clearance in elderly subjects [104].…”

Section: Ace Inhibitorsmentioning

confidence: 99%

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Age‐related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications

Mangoni

Jackson

2003

Brit J Clinical Pharma

1,383

911

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Advancing age is characterized by impairment in the function of the many regulatory processes that provide functional integration between cells and organs. Therefore, there may be a failure to maintain homeostasis under conditions of physiolog ical stress. The reduced homeostatic ability affects different regulatory systems in different subjects, thus explaining at least partly the increased interindividual variability occurring as people get older. Important pharmacokinetic and pharmacodynamic changes occur with advancing age. Pharmacokinetic changes include a reduction in renal and hepatic clearance and an increase in volume of distribution of lipid soluble drugs (hence prolongation of elimination half-life) whereas pharmacodynamic changes involve altered (usually increased) sensitivity to several classes of drugs such as anticoagulants, cardiovascular and psychotropic drugs. This review focuses on the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs.

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Section: Ace Inhibitorsmentioning

confidence: 99%

Section: Ace Inhibitorsmentioning

confidence: 99%

Age‐related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications

Mangoni

Jackson

2003

Brit J Clinical Pharma

1,383

911

View full text Add to dashboard Cite

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“…On days 1 and 7, the omapatrilat-induced blockade of the renin-angiotensin system was actually greater than that obtained with 20 mg fosinopril, which is a dose of fosinopril commonly recommended for the treatment of hypertension. 23 Yet, one has to take into account that only 1 dose of fosinopril was investigated.…”

Section: Hormonal Effectsmentioning

confidence: 99%

Renal Hemodynamic and Natriuretic Effects of Concomitant Angiotensin-Converting Enzyme and Neutral Endopeptidase Inhibition in Men

et al. 2002

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Abstract-This double-blind placebo-controlled study was designed to investigate the acute and sustained hormonal, renal hemodynamic, and tubular effects of concomitant ACE and neutral endopeptidase (NEP) inhibition by omapatrilat, a vasopeptidase inhibitor, in men. Thirty-two normotensive subjects were randomized to receive a placebo, omapatrilat (40 or 80 mg), or the fosinopril/hydrochlorothiazide (FOS/HCTZ; 20 and 12.5 mg, respectively) fixed combination for 1 week. Blood pressure, renal hemodynamics, urinary electrolytes and atrial natriuretic peptide excretion, and several components of the renin-angiotensin system were measured for 6 hours on days 1 and 7 of drug administration. When compared with the placebo and the FOS/HCTZ combination, omapatrilat induced a significant decrease in plasma angiotensin II levels (PϽ0.001 versus placebo; PϽ0.05 versus FOS/HCTZ) and an increase in urinary atrial natriuretic peptide excretion (PϽ0.01). These hormonal effects were associated with a significant fall in blood pressure (PϽ0.01) and a marked renal vasodilatation, but with no significant changes in glomerular filtration rate. The FOS/HCTZ markedly increased urinary sodium excretion (PϽ0.001). The acute natriuretic response to FOS/HCTZ was significantly greater than that observed with omapatrilat (PϽ0.01). Over 1 week, however, the cumulative sodium excretion induced by both doses of omapatrilat (PϽ0.01 versus placebo) was at least as great as that induced by the dose of FOS/HCTZ (PϭNS versus FOS/HCTZ). In conclusion, the results of the present study in normal subjects demonstrate that omapatrilat has favorable renal hemodynamic effects. Omapatrilat combines potent ACE inhibition with a sustained natriuresis, which explains its well-documented potent antihypertensive efficacy. Key Words: hemodynamics, renal Ⅲ sodium Ⅲ angiotensin-converting enzyme Ⅲ neutral endopeptidase Ⅲ omapatrilat Ⅲ vasopeptidase Ⅲ human A ngiotensin II is an important physiological modulator of renal function through its hemodynamic, glomerular, and tubular effects. 1 Hence, under most circumstances, interruption of the renin-angiotensin cascade with ACE inhibitors or angiotensin II type 1 receptor antagonists in humans promotes sodium excretion and increases renal blood flow without affecting glomerular filtration rate (GFR). As a result, filtration fraction decreases. 2 Atrial natriuretic peptide (ANP), the brain natriuretic peptide, and the C-type natriuretic peptide represent another family of peptides that have an important impact on renal function. 3,4 Indeed, in addition to a peripheral vasodilation, these peptides elicit diuresis and natriuresis, an attenuation of the release of renin and aldosterone and of the sympathetic nervous activity. 3 High plasma ANP and brain natriuretic peptide levels have been measured under several clinical conditions in which sodium and water retention occur, such as congestive heart failure or chronic renal failure. 3,4 In humans, the administration of exogenous ANP and the inhibition of natriuretic peptide...

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“…By decreasing blood flow to various organs (liver, kidneys and muscle), heart failure may slow the conversion of the prodrugs into active diacids, reduce metabolism and urinary excretion, and even alter the V ss' These changes have been observed in patients with cardiac failure, but they depend greatly on the degree of cardiac dysfunction and are more prominent in patients with severe CHF. [62,63] Gerckens et al [62] investigated the pharmacokinetics and pharmacodynamics of ramipril in 27 patients with global cardiac insufficiency NYHA III-IV (table IV). The total recovery oframipril and metabolites within 96 hours in urine was 39 ± 17.5%.…”

Section: Angiotensin Converting Enzyme Inhibitorsmentioning

confidence: 99%

Pharmacokinetic Changes in Patients With Oedema

Vrhovac

Sarapa

Bakran

et al. 1995

Clinical Pharmacokinetics

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The pharmacokinetics of furosemide (frusemide) in patients with oedema have been relatively well studied, but in many studies it is unclear whether the disease or the oedema per se has the major effect. The rate of absorption of oral furosemide in patients with oedema was decreased, but total bioavailability was almost unchanged. The peak serum concentration (Cmax) and time taken to achieve Cmax were either decreased or unchanged. Binding of furosemide to plasma proteins is lower in patients with congestive heart failure (CHF), decompensated liver cirrhosis (DLC) and nephrotic syndrome, probably as a result of hypoalbuminaemia. The elimination half-life (t1/2) can be unchanged (CHF, DLC) or prolonged (chronic renal failure: CRF). Plasma and renal clearance are reduced in patients with CRF and nephrotic syndrome, but are almost unchanged in CHF and DLC. Disease-induced disorders are mainly responsible for the alterations of furosemide pharmacokinetics in oedematous conditions, while the influence of oedema per se is probably not clinically relevant. The pharmacokinetics of digoxin have been studied in a small number of studies only. In patients with CHF, considerable interindividual differences have been found. Because digoxin has a narrow therapeutic window, this drug should be administered cautiously to oedematous patients. Theophylline has higher bioavailability in patients with oedema, with a significantly higher Cmax in patients with hepatic cirrhosis and CHF than in healthy volunteers (29 and 22%, respectively). Furthermore, clearance decreases and t1/2 increases in these patients. Angiotensin converting enzyme (ACE) inhibitors are often administered as prodrugs, and their pharmacokinetic profile could be influenced by the diseases that accompany oedematous states. However, the effect of oedema is difficult to discriminate from that of the disease. Individual ACE inhibitors are affected differently, but importantly the dosage of perindopril should be reduced in patients with CHF, while for most other ACE inhibitors the changes in pharmacokinetic parameters are clinically irrelevant. In conclusion, studies on pharmacokinetic changes in oedema are limited. Besides affecting absorption (after oral administration) and conversion of the prodrug to the active form, probably as a result of the associated disease, oedema has not been proven to cause any clinically relevant changes in pharmacokinetic parameters for individual drugs. However, further studies of this aspect of pharmacokinetics are needed.

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Pharmacokinetic Optimisation of Angiotensin Converting Enzyme (ACE) Inhibitor Therapy

Cited by 24 publications

References 39 publications

Age‐related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications

Age‐related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications

Renal Hemodynamic and Natriuretic Effects of Concomitant Angiotensin-Converting Enzyme and Neutral Endopeptidase Inhibition in Men

Pharmacokinetic Changes in Patients With Oedema

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