PHARMACOKINETICS AND PHARMACODYNAMICS OF TRANDOLAPRIL AFTER REPEATED ADMINISTRATION OF 2-MG TO YOUNG AND ELDERLY PATIENTS WITH MILD-TO-MODERATE HYPERTENSION

The new angiotensin-converting enzyme (ACE) inhibitor trandolapril 2 m g was administered daily for 10 consecutive days to young (mean age +/ - SEM 44.1 +/- 2.3 years; n = 10) and elderly (mean age +/- SEM 69.3 /- 0.9 years; n = 14) patients with mild-to-moderate hypertension. All groups had similar baseline blood pressures: mean 164/100 mm Hg. Maxi mal plasma ACE inhibition on day 10 and residual inhibition 24 h after the last dose was the same, irrespective of age: young, 85.2 and 57.4 %; elderly, 89.1 and 59.8%, respectively. There was no difference betw een the results on day 1 for the young and elderly groups. The absorpt ion of trandolapril was rapid(<1 h in all groups). The peak plasma con centration (C-max) and the area under the plasma concentration-time cu rve (AUC) were slightly higher in the older group, but the elimination half-life (t(1/2)) was the same, with no accumulation after repeat do sing. A steady-state plasma concentration of the active metabolite of trandolapril, trandolaprilat, was reached after 4 days in the two grou ps, with similar accumulation ratios(young, 1.48; elderly, 1.49). At s teady state, the C-max and AUC 0-24 h for trandolaprilat were similar in the two groups: young, 7.49 +/- 0.98 ng/ml and 82.27 +/- 6.95 ng/ml /h; elderly, 8.35 +/- 0.67 ng/ml/h and 96.75 +/- 5.67 ng/ml/h. Maximal reductions in systolic/diastolic blood pressures (at 6 h postdose) we re -14.1%/-16.1% in young patients and -14.6%/-17.5% for the elderly. Significant blood pressure reduction persisted for 48 h after the last dose. Tolerance was good, and no adverse events were reported. On the basis of the pharmacokinetic and pharmacodynamic data, we conclude th at there is no need to modify the dose of trandolapril in elderly hype rtensive (>65 years) patients.