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Vascular affinity of trandolapril
M Miyazaki1, T Kawamoto, H Okunishi
1Department of Pharmacology, Osaka Medical College, Takatsuki, Japan.
American Journal of Hypertension
|October 1, 1995
Summary
Trandolapril offers superior antihypertensive effects compared to enalapril due to its increased lipophilicity and potent inhibition of vascular angiotensin converting enzyme (ACE). This results in a longer duration of action and enhanced blood pressure reduction.
Area of Science:
- Pharmacology
- Cardiovascular Research
- Drug Discovery
Background:
- Trandolapril is an angiotensin converting enzyme (ACE) inhibitor used for hypertension.
- Enalapril serves as a chemical prototype for comparison.
- Understanding the pharmacokinetic and pharmacodynamic differences is crucial for optimizing antihypertensive therapy.
Purpose of the Study:
- To elucidate the pharmacologic basis for trandolapril's enhanced antihypertensive potency and duration compared to enalapril.
- To investigate the lipophilicity, in vitro potency, and in vivo efficacy of trandolapril and its metabolite.
Main Methods:
- Comparative analysis of lipophilicity between trandolapril/trandolaprilat and enalapril/enalaprilat.
- In vitro potency assessment of trandolaprilat versus enalaprilat.
- In vivo antihypertensive efficacy and duration studies in spontaneously hypertensive rats.
Main Results:
- Trandolapril and trandolaprilat demonstrated higher lipophilicity than enalapril and enalaprilat.
- Trandolaprilat exhibited three times greater in vitro potency than enalaprilat.
- Trandolapril was 10 times more effective and longer-acting in reducing blood pressure in rats.
Conclusions:
- Trandolapril's prolonged antihypertensive action is linked to sustained inhibition of vascular ACE.
- High lipophilicity may enhance tissue penetration and prolong the elimination half-life of trandolapril.
- Vascular tissue's lack of ACE induction contributes to trandolapril's sustained efficacy.