Drugs online research references
Gerontology. 1987;33 Suppl 1:17-23.
Population pharmacokinetics of lisinopril in hypertensive patients.
Thomson AH, Whiting B.
Department of Materia Medica, University of Glasgow, Stobhill General Hospital, UK.
If optimal dosage administration schedules are to be defined, the factors that influence the disposition of a drug in the population of patients who are likely to receive it should first be determined. Traditionally, separate groups of patients, each with different underlying disease, are given the drug and then detailed studies are performed to assess which groups have significantly different pharmacokinetic parameters and therefore require an adjustment in dose. An alternative approach, utilizing large groups of patients studied less intensively, will be described here. The analysis used the results of two multicenter trials of lisinopril: one in elderly (greater than 65 years) hypertensive patients and one in a group of hypertensive patients with impaired renal function (creatinine clearance rate less than 60 ml/min). Both protocols allowed for a stepwise increase in the dose of lisinopril until optimum control of BP was achieved. Required dosages ranged from 2.5 to 40 mg/day. During the course of therapy, regular trough concentrations were analyzed to assess compliance and a steady-state profile was determined during one dosage interval. Only patients who appeared to be compliant on the basis of multiple trough concentrations were used in the analysis. Data from a total of 53 patients were used, of whom 35 took part in the elderly study, and 18 in the renal study. There were 25 men and 28 women in this combined study group with ages ranging from 21 to 85 years (mean 65 years) and weights from 51 to 115 kg (mean 72 kg).(ABSTRACT TRUNCATED AT 250 WORDS)
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word match zestril online literature
Gerontology. 1987;33 Suppl 1:36-41.
Lisinopril treatment of hypertension in patients with impaired renal function.
Donohoe JF, Laher M, Doyle GD, Long C, Glover DR, Cooper WD.
Mater Hospital, Dublin, Ireland.
Lisinopril is a new, long-acting, nonsulfhydryl angiotension-converting enzyme (ACE) inhibitor that is excreted unchanged by the kidney. The antihypertensive efficacy and safety profiles of lisinopril were assessed in 24 patients (15 men, 9 women; mean age 52.3 years; range 21-75 years) with hypertension associated with impaired renal function (glomerular filtration rate GFR 60 ml/min or less), in an open study of 12 weeks' duration. Previous antihypertensive drugs were discontinued at entry into the study. Lisinopril was given orally once daily; the starting dose was 2.5 mg in patients with a GFR of less than 30 ml/min, and 5 mg in all other patients. The dosage of lisinopril was titrated upward to 40 mg daily according to BP response. A diuretic could then be added if hypertension was inadequately controlled. Twenty-three patients completed the study. Mean sitting BP was reduced from 177 +/- 21.2/106 +/- 9.1 mm Hg (mean +/- SD) at entry to the study to 145 +/- 21.4/88 +/- 8.3 mm Hg after 12 weeks of treatment (p less than 0.001). The median dose of lisinopril used was 10 mg (range 2.5-40 mg) and only 4 patients had a diuretic added to the lisinopril. Overall GFR was unchanged during the study: mean baseline value was 37 +/- 16.4 ml/min (range 10-60 ml/min) at the beginning of the study and 40 +/- 21.0 ml/min at the end. As in a previous pharmacokinetic study in similar patients, a tendency toward drug accumulation was noted only in those patients with the most severe renal impairment.(ABSTRACT TRUNCATED AT 250 WORDS)
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word match zestril online literature
Hypertension. 1988 Mar;11(3):230-8.
Inhibition of tissue angiotensin converting enzyme. Quantitation by autoradiography.
Sakaguchi K, Chai SY, Jackson B, Johnston CI, Mendelsohn FA.
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Inhibition of angiotensin converting enzyme (ACE) in serum and tissues of rats was studied after administration of lisinopril, an ACE inhibitor. Tissue ACE was assessed by quantitative in vitro autoradiography using the ACE inhibitor [125I]351A, as a ligand, and serum ACE was measured by a fluorimetric method. Following oral administration of lisinopril (10 mg/kg), serum ACE activity was acutely reduced but recovered gradually over 24 hours. Four hours after lisinopril administration, ACE activity was markedly inhibited in kidney (11% of control level), adrenal (8%), duodenum (8%), and lung (33%; p less than 0.05). In contrast, ACE in testis was little altered by lisinopril (96%). In brain, ACE activity was markedly reduced 4 hours after lisinopril administration in the circumventricular organs, including the subfornical organ (16-22%) and organum vasculosum of the lamina terminalis (7%; p less than 0.05). In other areas of the brain, including the choroid plexus and caudate putamen, ACE activity was unchanged. Twenty-four hours after administration, ACE activity in peripheral tissues and the circumventricular organs of the brain had only partially recovered toward control levels, as it was still below 50% of control activity levels. These results establish that lisinopril has differential effects on inhibiting ACE in different tissues and suggest that the prolonged tissue ACE inhibition after a single oral dose of lisinopril may reflect targets involved in the hypotensive action of ACE inhibitors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2832327&dopt=Abstract
word match zestril online literature
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