Population pharmacokinetics of lisinopril in hypertensive patients.
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)
Thomson
A H
AH
Department of Materia Medica, University of Glasgow, Stobhill General Hospital, UK.
Whiting
B
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics*; D004656:Enalapril / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood*; D007674:Kidney Diseases / Q000097:blood*; D017706:Lisinopril; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D017706:Lisinopril