Trandolapril: pharmacokinetics of single oral doses in healthy male volunteers.
The pharmacokinetics and dose proportionality of trandolapril, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated in 12 healthy male volunteers in a four-way randomized crossover study over the therapeutic dose range, 0.5-4 mg. Trandolapril is rapidly absorbed, with a single elimination half-life (t1/2) of 0.72 h, irrespective of dose. Peak plasma levels (Cmax) occurred at 0.5 h and were proportional to the dose, as was the area under the plasma concentration-time curve (AUC). Concentration of the active metabolite (trandolaprilat) increased with increasing doses but in a nonlinear fashion, probably owing to saturable plasma ACE binding. However, the Cmax and AUC values for trandolaprilat were directly proportional to the highest doses, 2 and 4 mg, suggesting linear kinetics for the trandolaprilat, which is not bound to ACE. Trandolapril showed linear kinetics but trandolaprilat showed some features of nonlinear kinetics, particularly at low doses.
Lenfant
B
B
Roussel UCLAF, Romainville, France.
Mouren
M
M
Bryce
T
T
De Lauture
D
D
Strauch
G
G
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril