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J Cardiovasc Pharmacol. 1987;9 Suppl 3:S69-71.
Lisinopril in elderly patients with hypertension.

Laher MS, Natin D, Rao SK, Jones RW, Carr P.

The antihypertensive efficacy and safety of lisinopril, a long-acting angiotensin-converting enzyme inhibitor, were assessed in 40 elderly patients (aged 65 years or over) with mild to moderate systolic/diastolic or isolated systolic hypertension, in an open study of 12 weeks' duration. Lisinopril was given orally in single daily doses. The starting dose was 5 mg in patients with glomerular filtration rate (GFR) of 30-60 ml/min and 10 mg in patients with GFR greater than 60 ml/min. The dose of lisinopril could be titrated upwards to a maximum of 40 mg daily according to blood pressure response. A thiazide diuretic was then added if blood pressure was not controlled. Thirty-six patients completed the study. Mean sitting blood pressure was significantly reduced by lisinopril treatment. There was no significant alteration in the heart rate, and postural hypotension did not occur. The median dose of lisinopril given was 20 mg daily (range 5-40 mg daily), and only two patients had a diuretic added to the lisinopril. One patient was withdrawn from the study because of unstable angina, and another was discontinued from lisinopril treatment because of anorexia and facial flushing. One patient was withdrawn after 8 weeks because of interruption of lisinopril therapy for a transurethral resection of the prostate, and one patient was lost to follow-up. No clinically significant haematological or biochemical changes were observed. The mean glomerular filtration rate was unchanged during the study. Proteinuria did not occur de novo, nor did established proteinuria increase. Thus lisinopril was well-tolerated and effective therapy in a group of elderly hypertensive patients.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2442557&dopt=Abstract




Pulm Pharmacol. 1992 Jun;5(2):103-9.
Rapid reversal of angiotensin converting enzyme inhibition by lisinopril in the perfused rabbit lung.

Rimar S, Gillis CN.

Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06510.

Lisinopril is a potent competitive inhibitor of purified rabbit lung ACE (dissociation t1/2 = 105 min). To examine reversibility of binding and ACE functional activity in situ, the single-pass extraction (E) of an 125I-lisinopril analogue (351A) and the hydrolysis of an ACE substrate, benz-phe-ala-pro (BPAP) were studied. Lungs were perfused at 50 ml/min with a Krebs-albumin (3%) solution. A bolus containing [14C]dextran, [3H]BPAP, and 351A was injected and (E)351A measured by multiple indicator dilution technique. BPAP metabolism (M) was reflected by the appearance of its hydrolysis product [3H]benz-phe in lung effluent. Control (E)351A was 66 +/- 5% (mean +/- SD, n = 6) and (M)BPAP was 69 +/- 9% (n = 6). Unlabeled lisinopril (30 nmol) in the bolus significantly reduced E(351A) and M(BPAP) to 16 +/- 16% and 3 +/- 3%, respectively. Ten minutes later E(351A) and M(BPAP) had returned to control values. Reduction of E(351A) was partially reversible and M(BPAP) completely reversible after 1 min. After recirculation with 0.25 mM lisinopril for 30 min, however, significant depression of E(351A) was evident for 60 min after exposure to lisinopril was discontinued. Thus, rapid as well as slowly reversible components of inhibition of ACE inhibitor binding can be demonstrated in the perfused rabbit lung.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1319250&dopt=Abstract




Br J Clin Pharmacol. 1989 Jan;27(1):57-65.
Lisinopril population pharmacokinetics in elderly and renal disease patients with hypertension.

Thomson AH, Kelly JG, Whiting B.

Department of Materia Medica, Stobhill General Hospital, Glasgow.

1. The population pharmacokinetics of lisinopril were investigated using data collected from two multicentre trials of lisinopril in the treatment of hypertension in elderly patients (n = 40) and patients with renal disease (n = 20). 2. Lisinopril was started at doses of 2.5-5 mg daily and increased at 2-4 weekly intervals as required for control of blood pressure. Steady-state concentration-time profiles were measured after at least 2 weeks at a constant dose. 3. All concentration-time data were analysed simultaneously using the program NONMEM and the influence of clinical factors on clearance/F and volume of distribution/F was tested. 4. Clearance was significantly influenced by creatinine concentration, age, weight and cardiac failure. No clinical features tested were found to influence volume of distribution. 5. The influence of renal function and cardiac failure on lisinopril clearance has been confirmed using a population pharmacokinetic analysis technique.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2539850&dopt=Abstract












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