The pharmacokinetics of amiloride-hydrochlorothiazide combination in the young and elderly

Summary

The pharmacokinetics of amiloride and hydrochlorothiazide were studied in 12 healthy young volunteers following a single dose of a fixed combination of amiloride and hydrochlorothiazide and in 11 elderly hypertensive patients at steady-state. Following modelling of the single dose data, simulated steady-state plasma concentrations for the 2 drugs were generated to examine the effect of age and/or hypertension on pharmacokinetics.

The apparent systemic plasma clearance for both amiloride and hydrochlorothiazide was significantly reduced in the elderly when compared to the young (from 753 to 325 ml·min⁻¹, amiloride; and from 418 to 157 ml·min⁻¹, hydrochlorothiazide). The plasma concentrations at steady state for both drugs were greatly increased in the elderly patients (Amiloride: from 7 to 25 ng·ml⁻¹, C_ss,max; from 2 to 8 ng·ml⁻¹, C_ss,min; and from 4 to 14 ng·ml⁻¹, C_av; Hydrochlorothiazide: from 184 to 651 ng·ml⁻¹, C_ss,max; from 31 to 121 ng·ml⁻¹, C_ss,min; and from 89 to 273 ng·ml⁻¹, C_av).

The decreased clearance of the diuretics in the elderly was believed due to deterioration of renal function, and there was a significant correlation between the plasma clearance of hydrochlorothiazide and creatinine clearance in both age groups (r=0.62, young;r=0.72, elderly).

As a result of the pharmacokinetic findings caution may be indicated in the clinical dosage of the diuretics particularly when in fixed dose combination.