Trandolapril. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in essential hypertension.
Trandolapril is a non-sulfhydryl prodrug which, after oral administration, is hydrolysed in the liver to its active diacid, trandolaprilat. Trandolaprilat inhibits the angiotensin converting enzyme (ACE) and displays similar pharmacodynamic properties to other ACE inhibitors, improving haemodynamic and cardiac parameters in patients with essential hypertension. Trandolapril 2 to 4mg once daily effectively controls blood pressure for at least 24 hours in patients with mild to moderate hypertension. In a small number of double-blind comparative trials, trandolapril had similar antihypertensive efficacy to that of atenolol, enalapril, hydrochlorothiazide, lisinopril and sustained release nifedipine, but was more effective than captopril. Combined therapy with trandolapril and hydrochlorothiazide or sustained release nifedipine had a significantly greater antihypertensive effect than either drug treatment alone. Further comparative trials are warranted to confirm these preliminary findings. The tolerability profile of trandolapril is similar to that of other ACE inhibitors, most adverse events being generally mild and transient in nature, and trandolapril lacks adverse effects on carbohydrate and lipid metabolism. Thus, trandolapril, with its favourable pharmacological profile and antihypertensive activity similar to that of agents currently used to treat patients with mild to moderate hypertension, is likely to provide a well tolerated option for the treatment of this disease. The results of ongoing and future clinical trials will determine its potential as a cardioprotective agent in patients following myocardial infarction.
Wiseman
L R
LR
Adis International Limited, Auckland, New Zealand.
McTavish
D
D
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D018849:Controlled Clinical Trials as Topic; D004361:Drug Tolerance; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007211:Indoles / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D015337:Multicenter Studies as Topic
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; C052035:trandolapril