Pharmacokinetics of Fosinopril and Hydrochlorothiazide in Healthy Elderly and Young Men
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Objective: This study evaluated the effect of advanced age on the single-dose and steady-state pharmacokinetics of the angiotensin converting enzyme inhibitor fosinopril along with the diuretic hydrochlorothiazide.
Design and Setting: Open-label, multiple-dose study in a hospital-based clinical study unit.
Study Participants: Twelve young (21 to 30 years) and 12 elderly (66 to 75 years) healthy men.
Interventions: Participants received a combination tablet of fosinopril 20mg and hydrochlorothiazide (HCTZ) 12.5mg as a single daily dose for a total of 6 doses. Drug concentrations were measured on days 1 and 7 by radioimmunoassay (fosinoprilat, the active diacid) and by HPLC (HCTZ) for calculation of first-dose and steady-state pharmacokinetic parameters.
Results: Fosinoprilat steady-state maximum serum concentration (Cmax) was somewhat higher in the elderly, but area under the serum concentration-time curve (AUC) and other pharmacokinetic parameters were similar in the young and elderly adults. As expected with age-related diminished renal function, HCTZ clearance was lower in the elderly, while its cumulative urinary excretion was similar in the two groups.
Conclusion: Advanced age is not accompanied by a clinically meaningful change in the pharmacokinetic profiles of fosinopril and HCTZ and does not warrant dose adjustment based on advanced age alone. The favourable pharmacokinetic feature of fosinopril of having dual (renal and hepatic) and compensatory elimination pathways is preserved in the elderly during combination therapy with HCTZ.
KeywordsAdis International Limited Hydrochlorothiazide HCTZ Fosinopril Clin Drug Invest
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