A comparison in young and elderly subjects of the pharmacokinetics and pharmacodynamics of single and multiple doses of benazepril.

Abstract

1. The pharmacokinetics and pharmacodynamics of single and multiple oral doses of the ACE inhibitor benazepril were investigated in young and elderly normotensive subjects. 2. Following multiple doses the trough concentrations were significantly higher in the elderly and the areas under the plasma concentration‐time curves (AUC0‐24) were significantly greater, by approximately 23%. 3. The fall in blood pressure tended to be greater in the elderly subjects but this is likely to be attributable to their higher initial blood pressures, although it may reflect the small differences in pharmacokinetics. 4. The age related differences in kinetics and dynamics following multiple dosing are quantitatively similar to those obtained with single doses. However, there appears to be a quantitative difference between benazepril and other ACE inhibitors in that the age related increases were of a relatively smaller magnitude.

Optimal Dosage of ACE Inhibitors in Older Patients

“…Macdonald et al,l25,27] described this with benazepril and enalapril, and attributed it to higher initial blood pressure levels. Similar findings were described in another study of intravenous enalaprilat and oral enalapril.…”

“…Reduction in muscle and organ mass, accompanied by increased adipose tissue mass, decreases the Benazepril S10 Kaiser et al [26] Benazepril S10 Macdonald et al [27] Benazepril M10 Creasey et al [ 28 1 Captopril S 100 Williams et al [29] Cilazapril S1 Hockings et al [3O] Enalapril S10 Macdonald et al [25] Enalapril S10 Levinson et al [31] Fosinopril S10 Cirillo et al [32] Lisinopril S20 Gautam et al [ Ramipril S20 Grass et al [38] Spirapril S25 Arner et al [39] Trandolapril S2 M2…”

Impact of Disease States on the Pharmacokinetics and Pharmacodynamics of Angiotensin‐Converting Enzyme Inhibitors

“…Interpreting hemodynamic outcomes of studies in the elderly is particularly difficult because of a number of issues, including generally higher resting blood pressures, which can confound the results. Both benazepril and enalapril have demonstrated greater blood pressure reduction in elderly patients compared to younger ones; however, this response was not statistically significant when adjusted for baseline blood pressure 82,83 . In another study, elderly and young patients were given enalapril, enalaprilat, or placebo, and the fall in blood pressure was significantly greater in the elderly for both active treatments 5 .…”

Simultaneous and rapid quantitation of benazepril and benazeprilat in human plasma by high performance liquid chromatography with ultraviolet detection

“…A reliable quantitative method that allows a simultaneous determination of the concentration of BZL and BZT in plasma is thus needed. Several analytical methods have been developed, such as high-performance liquid chromatography (HPLC), capillary electrophoresis and an enzymatic method coupled with HPLC or liquid scintillation counting [7,[9][10][11][12]15,16,[18][19][20][21]. Most of these methods, however, are applicable for the purity evaluation of benazepril in bulk drugs and pharmaceutical dosage forms.…”

“…Studies have been performed to evaluate the pharmacokinetics of BZL in healthy subjects [7,[9][10][11][12][13][14], the elderly [15] and patients with hypertension, major proteinuria, or liver cirrhosis [7,16,17]. Sun et al [9] reported that after a single oral administration of 10 mg benazepril hydrochloride tablet to 12 healthy male Caucasians in South Wales, UK, the mean area under the plasma concentration-time curve (AUC 0-4 h ), maximum plasma concentration (C max ) and time to C max (t max ) values for BZL were 140 ng h/mL, 149 ng/mL, and 0.6 h, respectively; while the mean AUC 0-24 h , C max , and t max values for BZT were 1410 ng h/mL, 257 ng/mL, and 1.5 h, respectively.…”