Furosemide kinetics and dynamics in aged patients

Area of Science:

• Pharmacology
• Geriatric Medicine
• Nephrology

Background:

• Furosemide (F) is a commonly prescribed diuretic in the elderly population.
• Age-related physiological changes may impact drug disposition and efficacy.
• Understanding these changes is crucial for safe and effective geriatric pharmacotherapy.

Purpose of the Study:

• To investigate age-related alterations in furosemide (F) pharmacokinetics and pharmacodynamics in geriatric patients.
• To determine if these changes can be predicted or explained by specific patient characteristics.
• To assess the relationship between furosemide's effects and renal function in the elderly.

Main Methods:

• Intravenous furosemide (F) injection administered to geriatric patients (aged 70-93 years).
• Kinetics and diuretic effects were systematically measured and analyzed.
• Correlation analysis performed between pharmacokinetic parameters, diuretic effects, and patient characteristics like endogenous creatinine clearance (ECC) and plasma creatinine.

Main Results:

• Geriatric patients exhibited a slightly enlarged volume of distribution, diminished total body clearance, decreased renal clearance (40 +/- 18 ml/min), and a prolonged elimination half-life (180 +/- 87 min) for furosemide (F).
• Furosemide (F) effects were maintained only when accounting for reduced renal delivery and glomerular filtration rate.
• Renal F clearance and overall F effects were best predicted by endogenous creatinine clearance (ECC) and plasma creatinine levels.

Conclusions:

• Age-dependent and disease-dependent decreases in glomerular filtration and renal secretion reduce furosemide (F) efficacy in the elderly.
• Endogenous creatinine clearance (ECC) is a key predictor of furosemide (F) disposition and effects in geriatric patients.
• Standard dosing of furosemide (F) may lead to diminished therapeutic outcomes in the elderly due to altered pharmacokinetics and pharmacodynamics.