Age and the pharmacodynamics of angiotensin converting enzyme inhibitors enalapril and enalaprilat.

Aa, Ajayi; Hockings, N.; Reid, JL

doi:10.1111/j.1365-2125.1986.tb05206.x

Cited by 25 publications

(13 citation statements)

References 30 publications

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“…The findings of reduced clearance, greater AUC and reduced distribution volume may partly explain the greater hypotensive effect and prolonged converting enzyme inhibition we have observed in elderly subjects (Ajayi et al, 1986). We detected no age related alteration in the sensitivity of plasma ACE to inhibition.…”

Section: Discussionsupporting

confidence: 48%

“…We detected no age related alteration in the sensitivity of plasma ACE to inhibition. Thus, sensitivity of ACE is unlikely to underlie the pharmacodynamic differences observed between the two groups (Ajayi et al, 1986). The full therapeutic implication of the findings from this single dose study must await further multiple dose studies in the elderly.…”

Section: Discussionmentioning

confidence: 84%

“…This work was presented previously as a communication to the British Pharmacological Society (Hockings et al, 1985). The effects of enalapril and enalaprilat on blood pressure and autonomic and endocrine function in these subjects are described separately (Ajayi et al, 1986 …”

Section: Introductionmentioning

confidence: 99%

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Age and the pharmacokinetics of angiotensin converting enzyme inhibitors enalapril and enalaprilat.

Hockings¹,

Aa²,

Reid³

1986

Brit J Clinical Pharma

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The pharmacokinetics of angiotension converting enzyme (ACE) inhibitors enalapril (10 mg orally) and its active metabolite, enalaprilat (10 mg intravenously) were studied in nine young healthy volunteers aged 22‐30 years and nine sex matched elderly subjects aged 65‐73 years. After both drugs, a biexponential curve was fitted to the decline in plasma enalaprilat concentration. Area under the plasma concentration‐time curve (AUC) was greater in the elderly for both drugs. Clearance (CL) and clearance/bioavailability (CL/F) were less in the elderly for enalaprilat and enalapril, respectively. There was no difference in F between young (0.62 +/‐ 0.16) and elderly subjects (0.61 +/‐ 0.15). Enalaprilat CL and enalapril CL/F were significantly and positively correlated to endogenous creatinine clearance. There was a significant difference in the weight corrected volume of distribution at steady state after enalaprilat between the young and elderly (P less than 0.02). The relationship between plasma enalaprilat concentrations and percentage ACE inhibition, using the Hill equation, showed no difference in the sensitivity to ACE inhibition between the young and the elderly group. The pharmacokinetic differences observed are likely to be related to an age dependent decline in renal function as well as changes in body composition. Kinetic differences partly explain the greater pharmacodynamic response in the elderly.

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 84%

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Age and the pharmacokinetics of angiotensin converting enzyme inhibitors enalapril and enalaprilat.

Hockings¹,

Aa²,

Reid³

1986

Brit J Clinical Pharma

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“…This has been postulated as being a reflection of the lower prevalence of hypertension associated with elevation of plasma renin activity in the elderly patient [4]. Based on this premise, it has been postulated that inhibitors of angio tensin-converting enzyme (ACE) would not be of particular value in treating elderly hypertensive patients [5], However, singleand multiple-dose studies with the ACE in hibitor enalapril maleate have shown that elderly patients respond with a greater fall in BP than do younger patients, although, when corrected for the higher starting BP in the elderly patient, the effect may be similar [6,7], The ACE inhibitors enalapril and lisinopril have both been shown to have significant anti hypertensive activity in elderly patients with hypertension [8. 9], although no direct com parisons across the entire age spectrum have been performed.…”

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confidence: 99%

Influence of Age on Blood Pressure Response to Enalapril

Cooper¹,

Glover²,

Kimber³

1987

Gerontology

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Based on prevailing hypotheses about the role of renin in essential hypertension, both Laragh and Buhler independently predicted that angiotensin-converting enzyme (ACE) inhibitors would become less effective with increasing age, as elderly hypertensive patients tend to have low plasma renin activity. We have investigated this situation in a large postmarketing surveillance study with enalapril. Following a 2-week no-treatment period, a total of 11,710 patients with essential hypertension received 10–20 mg of enalapril once daily for 6 weeks. BP was measured on two occasions prior to enalapril treatment, and on two occasions during enalapril treatment (after 2 and 6 weeks). Enquiry for symptom events was also made on each of these four occasions. Systolic BP (SBP) prior to enalapril treatment rose steeply with increasing age, whereas diastolic BP (DBP) rose only very slightly with age and reached a plateau by the 5th decade. The fall in SBP in response to enalapril increased with increasing age, but DBP was relatively uninfluenced by age. However, when corrected for initial BP, the percentage changes in both SBP (13%) and DBP (14%) were not different across the age range studied. Prior to receiving enalapril, 67.8% of patients were reporting symptoms, and this showed a positive correlation with age. During enalapril therapy, the overall level of symptom events reported fell significantly in all age groups (35.0%) but more so in the elderly, such that at the end of the study no significant age-related difference was detected. In all age groups, more than half of the events reported during enalapril therapy were of an improvement in general well-being. This study further supports the view that, contrary to earlier predictions, ACE inhibitors are at least as effective in elderly hypertensive patients as in younger patients. This may also be accompanied by a significant reduction in the number of adverse events reported, particularly in the most elderly. As age and BP are both continuous variables and are related to each other, they must be considered as continuous variables in the assessment of treatment effects. To use arbitrary definitions for the elderly (e.g. > 60 years or > 65 years) will only serve to exaggerate age-related phenomena and may lead to inappropriate recommendations for drug use.

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“…However, it is now apparent, both from small, detailed studies of the kinetics and dynamics of ACE inhibi tors in older subjects [23][24][25] and from ex tensive clinical experience, that these drugs are effective and well tolerated either alone or in combination with diuretics in the el derly [26,27], Minor age-related pharmaco kinetic differences have been reported. These include a predictable reduction in elimination by the kidney [23] and minor changes in distribution, volume, and bio availability [25], The magnitude of blood pressure fall after acute dosing may be greater in elderly normotensive subjects than in the young [24,25]. Interpreting these re sults poses some difficulty because of differ ent baseline values and the fact that the per centage change in blood pressure may be the same.…”

Section: Ace Inhibitors In the Elderlymentioning

confidence: 99%

Present Aspects and Future Developments with ACE Inhibitors

Reid¹

1989

Cardiology

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With several angiotensin-converting enzyme (ACE) inhibitors currently in clinical use for the treatment of hypertension, and many others under development, potential applications of these drugs have expanded. When ACE inhibitors lower blood pressure they do not induce tachycardia. Contrary to expectations, ACE inhibitors have been found extremely useful in treating hypertension in the elderly and also patients with heart failure. Plasma renin assay is not always helpful in determining the optimum dosage range. While no evidence has yet been found for differential effects of these drugs in man, tissue-sensitive ACE inhibitors could be of considerable clinical interest.

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Age and the pharmacodynamics of angiotensin converting enzyme inhibitors enalapril and enalaprilat.

Cited by 25 publications

References 30 publications

Age and the pharmacokinetics of angiotensin converting enzyme inhibitors enalapril and enalaprilat.

Age and the pharmacokinetics of angiotensin converting enzyme inhibitors enalapril and enalaprilat.

Influence of Age on Blood Pressure Response to Enalapril

Present Aspects and Future Developments with ACE Inhibitors

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