Amiloride disposition in geriatric patients: importance of renal function.

Abstract

1. The absorption and disposition of the potassium sparing diuretic amiloride were determined in nine elderly patients aged 71 to 87 years and in eight young (25 to 38 years) subjects following oral administration of 5 mg amiloride HCl daily to steady‐state. 2. The maximum and steady‐state plasma amiloride concentrations were significantly (P less than 0.05 and P less than 0.001) higher in the elderly patients. The renal clearance of amiloride was lower in the elderly than in young subjects (102 +/‐ 36 ml min ‐1 vs 300 +/‐ 64 ml min‐1, P less than 0.001) as was the urinary excretion of amiloride (36 +/‐ 13 vs 62 +/‐ 18% of the dose, P less than 0.01). 3. The steady‐ state plasma amiloride concentration correlated significantly (r2 = 0.61, P less than 0.001) with amiloride renal clearance and with creatinine clearance (r2 = 0.59, P less than 0.001). There was a very strong positive correlation between renal amiloride clearance and creatinine clearance (r2 = 0.76, P less than 0.001). The slope of the regression line was 2.5 indicating substantial proximal tubular secretion of amiloride. 4. Sodium and potassium excretion, along with urine volume were significantly (P less than 0.05) lower in the elderly (by 39, 45 and 34% respectively). 5. The disposition of amiloride was highly dependent on renal function, with higher plasma amiloride concentrations in the elderly reflecting diminished renal function. The dose of amiloride should be titrated to individual response, and the lower potassium excretion in the elderly patients suggests that the dose of amiloride could be reduced in this group of patients.

Age‐related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications

“…Kidney Reduction in renal function in elderly subjects, particularly glomerular filtration rate, affects the clearance of many drugs such as water-soluble antibiotics [69,70], diuretics [71], digoxin [72], water-soluble badrenoceptor blockers [73], lithium [74], and nonsteroidal anti-inflammatory drugs [75,76]. The clinical importance of such reductions of renal excretion is dependent on the likely toxicity of the drug.…”

Adverse Drug Reactions An Overview of Special Considerations in the Management of the Elderly Patient

“…However, the incidence of hyperkalaemia with these drugs increases with age, particularly in the presence of renal impairment (Lawson 1974). Increased plasma amiloride concentrations (Sabanathan et al 1987;Somogyi et al 1990) associated with age-related reductions in urinary potassium excretion have recently been demonstrated. No data were available on serum potassium concentrations (Somogyi et al 1990).…”

Pharmacokinetic dosage guidelines for elderly subjects

“…1.33/1.34, 1.1 0.64/1.07, 1.1 [46,47] Amikacin 0.02 1.6 0.7 [48] Amiloride * < 0.5 5.83 4.94 [49] Amiodarone 1! 2.6 1.7 [50] Amitriptyline 1 (1!)…”