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, Css,max; from 2 to 8 ng·ml−1, Css,min; and from 4 to 14 ng·ml−1, Cav; Hydrochlorothiazide: from 184 to 651 ng·ml−1, Css,max; from 31 to 121 ng·ml−1, Css,min; and from 89 to 273 ng·ml−1, Cav).
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.
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References
Triggs EJ, Nation RL (1975) Pharmacokinetics in the aged: A review. J Pharmacokinet Biopharm 3: 387–418
Crooks J, O'Malley K, Stevenson IH (1976) Pharmacokinetics in the elderly. Clin Pharmacokient 1: 280–296
Vestal RE (1978) Drug use in the elderly: A review of problems and special considerations. Drugs 16: 358–382
Greenblatt DJ, Sellers EM, Shader RI (1982) Drug disposition in old age. New Engl J Med 306: 1081–1087
Williamson J (1979) Adverse reactions to prescribed drugs in the elderly — a multicentre investigation. In: Crooks J, Stevenson IH (eds) Drugs and the elderly. Macmillan, London, pp 239–246
Sabanathan K, Castleden CM, Adam HK, Ryan J, Fitzsimons TJ (1987) A comparitive study of the pharmacokinetics of atenolol, hydrochlorothiazide and amiloride in normal young and elderly subjects and elderly hypertensive patients. Eur J Clin Pharmacol 32: 53–60
Bourne DWA (1987) MultiForte, a microcomputer program for modelling and simulation of pharmacokinetic data. Comput Methods Programs Biomed 23: 277–281
Cockcroft DW, Gault MW (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16: 31–41
Gibaldi M, Perrier D (1982) Pharmacokinetics (2nd edn). Dekker, New York, p 138
May FE, Stewart RB, Hale WE, Marks RG (1982) Prescribed and nonprescribed drug use in an ambulatory elderly population. South Med J 75: 522–528
Beermann B, Groschinsky-Grind M (1977) Pharmacokinetics of hydrochlorothiazide in man. Eur J Clin Pharmacol 12: 297–303
Barbhaiya RH, Craig WA, Corrick-West HP, Welling PG (1982) Pharmacokinetics of hydrochlorothiazide in fasted and nonfasted subjects: a comparison of plasma level and urinary excretion methods. J Pharm Sci 71: 245–248
Avery's drug treatment — Principles and practice of clinical pharmacology and therapeutics, 3rd edn (1987) Speight TM (ed). ADIS Press, Sydney, p 1376
Spahn H, Reuter K, Mutschler E, Gerok W (1987) Pharmacokinetics of amiloride in renal and hepatic disease. Eur J Clin Pharmacol 33: 493–498
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Ismail, Z., Triggs, E.J., Smithurst, B.A. et al. The pharmacokinetics of amiloride-hydrochlorothiazide combination in the young and elderly. Eur J Clin Pharmacol 37, 167–171 (1989). https://doi.org/10.1007/BF00558226
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DOI: https://doi.org/10.1007/BF00558226