Determination of benazepril, a new angiotensin-converting enzyme inhibitor, and its active metabolite, benazeprilat, in plasma and urine by capillary gas chromatography-mass-selective detection

Sioufi, A.; Pommier, F.; Kaiser, Guenther; Dubois, J.P.

doi:10.1016/0378-4347(88)80082-3

Cited by 41 publications

(13 citation statements)

References 3 publications

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“…Benazepril and benazeprilat were assayed by gas chromatography-mass spectometry [8]. In general, benazepril was well tolerated by both young and elderly subjects, although one elderly female subject experienced symptomatic orthostatic hypotension after the initial 10 mg dose of benazepril.…”

Section: Laboratory Methodsmentioning

confidence: 99%

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

Macdonald

Elliott

Hughes

et al. 1993

Brit J Clinical Pharma

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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.

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Section: Laboratory Methodsmentioning

confidence: 99%

“…In an open study, each subject received 10 mg benazepril daily for 8 24,48 and 72 h post-dose. Supine and erect blood pressure were measured in duplicate by Sentron semiautomated sphygmomanometer (Sentron, Bard Bimedical) at the same times as the plasma concentration measurements.…”

Section: Methodsmentioning

confidence: 99%

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

Macdonald

Elliott

Hughes

et al. 1993

Brit J Clinical Pharma

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“…Plasma benazeprilat concentrations were measured using a GC-MS with mass selective detection [6,21]. Blood samples were collected before and 2 hr after oral administration of benazepril, which was the time for peak concentration of benazeprilat [6,7] on the 1st to 5th, 8th, 10th, and 15th days of administration.…”

Section: Methodsmentioning

confidence: 99%

Plasma Concentrations of an Angiotensin-Converting Enzyme Inhibitor, Benazepril, and Its Active Metabolite, Benazeprilat, after Repeated Administrations of Benazepril in Dogs with Experimental Kidney Impairment.

Kitagawa

Eguchi

Kitoh

et al. 2000

The Journal of Veterinary Medical Science

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ABSTRACT. In order to examine the safety of an angiotensin-converting enzyme (ACE) inhibitor in dogs with impaired renal excretion route, benazepril was administered orally, and plasma concentrations of benazeprilat, the active metabolite of benazepril, were determined in dogs with renal mass reduction (1/4th kidney) created by right-side nephrectomy and ligation of branches of the left renal arteries. Five dogs were administered benazepril orally at a given dose (0.5 mg/kg body weight) and 4 other dogs received 20 times that dose (10 mg/kg body weight) once daily for 15 consecutive days before (intact kidney period) and after (1/4th kidney period) creation of kidney impairment. Six control dogs received surgical treatment, but no drug. After creating a 1/4th kidney, plasma urea nitrogen and creatinine concentrations increased to approximately 30 mg/dl and 2.0 mg/dl, respectively, and renal plasma flow and glomerular filtration rate decreased to 37% and 30% of pre-treatment values, respectively. However, these parameters did not change significantly during the 1/4th kidney period both in the 0.5 mg/kg and 10 mg/kg groups. In the 0.5 mg/kg group, plasma benazeprilat concentrations increased to approximately 20 ng/ml to 340 ng/ml 2 hr after each administration, and there were no significant differences between the plasma benazeprilat concentrations during the intact and 1/4th kidney periods. In the 10 mg/kg group, plasma benazeprilat concentrations varied in the individual dog, but did not increase with the days of administration, and were not significantly different on each administration day between the intact and 1/4th kidney periods in either dose group. The AUCs(0-24) of plasma benazeprilat concentrations determined on the 15th administration day were not different between the intact and 1/4th kidney periods in dogs of either dose group. Plasma ACE activities decreased after drug administration in dogs of both groups. Benazepril seemed to have a high safety, and the adjustment of dosage regimen might not be needed in dogs with mild to moderate renal function impairment because the drug was excreted both from the kidneys and liver.-KEY WORDS: angiotensin-converting enzyme inhibitor, benazepril, canine, plasma concentration, renal impairment.

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“…RBC and WBC were counted with an automated cell counter (Celltac MEK-5155, Nihon Kohden Corporation, Tokyo, Japan), and plasma biochemicals (urea nitrogen, creatinine, alanine aminotransferase (ALT), alkaline phosphatase (ALP), sodium, potassium, chloride, total protein, and albumin) were determined by the dry-chemistry method (Dry-Chem 5500V and 800V, Fuji Photo-Film Co., Ltd., Tokyo, Japan). Plasma benazepril and benazeprilat concentrations were determined by a GC-MS method with mass selective detection [7,16]. Plasma ACE activity was determined by the Kasahara method [5].…”

Section: Dogsmentioning

confidence: 99%

An Angiotensin Converting Enzyme Inhibitor, Benazepril Can Be Transformed to an Active Metabolite, Benazeprilat, by the Liver of Dogs with Ascitic Pulmonary Heartworm Disease

Kitagawa

Ohba

Kuwahara

et al. 2003

The Journal of Veterinary Medical Science

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ABSTRACT. To examine whether an angiotensin converting enzyme (ACE) inhibitor, benazepril, can be transformed to the active metabolite, benazeprilat, by severely injured liver of dogs with ascitic heartworm disease, benazepril hydrochloride was administered orally to dogs once daily for 7 consecutive days at a dose rate of 0.29 mg/kg to 0.63 mg/kg of body weight, and plasma benazepril and benazeprilat concentrations were determined on the 1st and 7th administration days. In 7 dogs with ascitic pulmonary heartworm disease, plasma benazeprilat concentrations tended to be higher than in 7 control dogs both on the 1st and 7th administration days. The peak concentration and area under the concentration-time curve tended to be greater in dogs of the ascites group than in control dogs, but the statistics could not detect significant differences in the time to peak concentration and t 1/2 between the control and ascites groups. Plasma ACE activities decreased after administration of benazepril. In dogs with ascitic heartworm disease, benazepril was readily transformed to benazeprilat by the liver, and was effective for suppression of plasma ACE activity.

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Determination of benazepril, a new angiotensin-converting enzyme inhibitor, and its active metabolite, benazeprilat, in plasma and urine by capillary gas chromatography-mass-selective detection

Cited by 41 publications

References 3 publications

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

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

Plasma Concentrations of an Angiotensin-Converting Enzyme Inhibitor, Benazepril, and Its Active Metabolite, Benazeprilat, after Repeated Administrations of Benazepril in Dogs with Experimental Kidney Impairment.

An Angiotensin Converting Enzyme Inhibitor, Benazepril Can Be Transformed to an Active Metabolite, Benazeprilat, by the Liver of Dogs with Ascitic Pulmonary Heartworm Disease

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