Pharmacokinetic and antihypertensive profile of amlodipine and felodipine-ER in younger versus older patients with hypertension.
To evaluate the impact of age on the pharmacokinetics and blood pressure (BP) responses of a dihydropyridine (DHP) with large versus small first-pass metabolism in hypertensive subjects, younger (n = 28) and older (n = 35) patients with hypertension were randomized to placebo, felodipine-ER 5 mg/d, or amlodipine 5 mg/d. In the young subjects, the first dose of either DHP did not decrease BP and chronic dosing decreased BP by approximately 10 mm Hg, which had disappeared by 24 hours. In the older group, felodipine-ER decreased systolic BP by approximately 10 mm Hg after the first dose and by approximately 20 mm Hg after chronic dosing, which had disappeared after 24 hours. The first dose of amlodipine caused a gradual fall in BP and chronic dosing by approximately 20 mm Hg and still by approximately 10 mm Hg at 120 hours. Older subjects showed approximately 30% higher area under the concentration–time curves and plasma concentrations of felodipine and amlodipine, but (apparent) elimination half-lives did not differ between younger and older subjects. The chronic antihypertensive responses correlated well with both plasma levels and pretreatment BP. Age has only a modest impact on the pharmacokinetics of amlodipine and felodipine-ER but markedly affects the BP response to the first dose of either DHP and the duration of action after chronic dosing of amlodipine.
Leenen
Frans H H
FH
Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. fleenen@ottawaheart.ca
Coletta
Elizabeth
E
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D017311:Amlodipine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003692:Delayed-Action Preparations; D015736:Felodipine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D055815:Young Adult
D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D017311:Amlodipine; D015736:Felodipine