| Autor: |
King, J. N., Maurer, M., Morrison, C. A., Mauron, C., Kaiser, G. |
| Předmět: |
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| Zdroj: |
Xenobiotica; Aug97, Vol. 27 Issue 8, p819-829, 11p |
| Abstrakt: |
1. The pharmacokinetics of the angiotensin-converting-enzyme (ACE) inhibitor benazepril were evaluated in eight healthy Beagle dogs. Benazepril was administered orally at a dosage of 7 5 mg (about 0 5 mg kg) both as a single dose and then once daily for 14 consecutive days. The prodrug, benazepril, and its active metabolite, benazeprilat, were measured in plasma using a gas chromatography mass-spectrometry method with massselective detection. 2. Benazepril appeared quickly in the plasma ( t 0 5 h) and was rapidly eliminated by max metabolism to benazeprilat. Peak benazeprilat concentrations were attained later ( t max 1 25 h) and declined biphasically with a rapid elimination phase ( t lambda 1 1 and 1 7 h after single and the last repeated dose respectively) followed by a terminal elimination phase ( t lambda 11 7 and 19 0 h after single and repeated dose respectively). The mean residence time z for benazeprilat was 15 2 h after the single dose and 17 4 h after the 14th dose. 3. Repeated administration of benazepril produced moderate bioaccumulation of benazeprilat; the ratio of AUC 's after the 14th dose as compared with the single dose h was 1 47, equivalent to a half-life for accumulation ( t ) of 14 6 h. Steady-state acc benazeprilat concentrations at peak ( C ) and trough ( C ) were reached within three max min doses. 4. The pharmacodynamics of benazepril were assessed by measurement of plasma ACE activity. After both single doses and at steady-state, benazepril produced inhibition of ACE activity in all dogs that was maximal at peak effect ( E 100%) and long-lasting max ( 85% inhibition was present at 24 h). The long duration of action of benazepril on plasma ACE is due to the presence of the terminal elimination phase of benazeprilat, even though most of the metabolite is rapidly eliminated from the plasma. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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