The effects of age on the pharmacokinetics and pharmacodynamics of single oral doses of benazepril and enalapril.

Abstract

1. Eighteen healthy, normotensive subjects (nine young and nine elderly) participated in a double‐blind, 3‐way, crossover study to compare aspects of the pharmacokinetics and pharmacodynamics of single oral doses of 10 mg benazepril, 10 mg enalapril and placebo. 2. The hypotensive effect was similar after both drugs but the absolute reductions were greater in the elderly who had higher initial levels of blood pressure. 3. The AUCs for both benazeprilat and enalaprilat were higher in the elderly but by a significantly greater amount for enalaprilat (+ 113% vs 40%; P < 0.01). 4. The AUCs for both drugs tended to be highest in subjects with the lowest creatinine clearance. 5. The changes in kinetics and dynamics observed in the elderly after benazepril are qualitatively similar to those with other ACE inhibitors. The clinical significance of the quantitative differences requires further investigation.

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

“…The effects of age on the single dose pharmacokinetics and pharmacodynamics of oral benazepril have been reported previously in a comparative study with enalapril [3]. In brief, there were pharmacokinetic differences between young and elderly subjects for both enalapril and benazepril.…”

“…As with the single dose study [3], there were significant differences between the two age groups in the steady state disposition of benazeprilat. The trough concentrations were significantly higher in the elderly, 37 nmol 1-1 [9].…”

Optimal Dosage of ACE Inhibitors in Older Patients

“…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…”

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.…”