Pharmacologic profile of trandolapril, a new angiotensin-converting enzyme inhibitor.

Trandolapril is a newly developed angiotensin-converting enzyme (ACE) inhibitor that is rapidly hydrolyzed mainly in the liver to its biologically active metabolite trandolaprilat. The time to reach peak plasma concentrations of trandolaprilat is about 6 hours; the effective plasma half-life of accumulation at steady state is 24 hours. The active metabolite trandolaprilat has very high lipophilicity in comparison with other ACE inhibitors, which should contribute to an improved tissue penetration of the substance. The very high affinity of trandolaprilat to the ACE and the corresponding low dissociation rate are probably the two main reasons for the prolonged duration of action. The high potency of trandolaprilat in ACE inhibition is reflected by its low IC50 (concentration needed to inhibit 50% of the enzyme activity). With repeated once-daily administration of trandolapril, plasma ACE activity was reduced in a dose-dependent fashion, but increasing the dose beyond 2 mg did not further reduce angiotensin II levels, apparently because of the compensatory increase in plasma renin levels. Therefore trandolapril in a dose of 2 mg once a day reduces blood pressure consistently throughout the 24 hour-period after intake. Because of its particularly long half-life, trandolapril, probably more than any other drug of its class, can be considered a true, once-a-day antihypertensive drug.