Summary
Six normal young and six normal elderly volunteers and six elderly hypertensive patients took part in an acute and chronic dose study of a combination capsule containing atenolol (50 mg), hydrochlorothiazide (25 mg) and amiloride (2.5 mg) designed for the treatment of hypertension. No difference in any of the drug pharmacokinetic parameters could be detected between the hypertensives and the normal elderly subjects. The bio-availability and the 24-h blood concentrations of all three drugs, half-life of atenolol and amiloride and the peak concentration of hydrochlorothiazide was significantly greater in the elderly. The 24-h blood concentrations of atenolol and hydrochlorothiazide did not alter with chronic dosing, but amiloride concentrations were significantly higher at this time in all groups. A significant fall in the blood pressure was observed in the hypertensive group. Heart rate fell more in the normal and hypertensive elderly subjects than in the young. The combination has shown to be an effective and well tolerated antihypertensive in the elderly patient with a 24-h duration of action.
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Chaudhry AY, Bing RF, Castleden CM, Swales JD, Napier CJ (1984) The Effect of ageing on the response to frusemide in normal subjects. Eur J Clin Pharmacol 27: 303–306
Reeves PR, McAinsh J, McIntosh DAD, Winrow MJ (1978) Metabolism of atenolol in man. Xenobiotica 8 [5]: 313–320
Rubin PC, Scott JWP, McLean K et al. (1982) Atenolol disposition in young and elderly subjects. Br J Clin Pharmacol 13: 235–237
Barber HE, Hawksworth GM, Peartrie JL et al. (1981) Pharmacokinetics of atenolol and propranolol in young and elderly subjects. Br J Clin Pharmacol 11: 118p-119p
Scales B, Copsey PB (1975) The gas chromatographic determination of atenolol in biological samples. J Pharm Pharmacol 27: 430–433
Molholm-Hansen J, Kampmann J, Laursen H (1980) Renal excretion of drugs in elderly. Lancet 1: 1170
O'Malley K, Crookes J, Duke E, Stevenson IH (1971) Effects of age and sex on human drug metabolism. Br Med J 3: 607–609
McAinsh J, Bastain N, Young J, Harry JD (1981) Bioavailability in men of atenolol and chlorthalidone from a combination formulation. Biopharm Drug Dispos 2: 147–156
Godbillon J, Gerardin A, John VA, Theobold N (1983) Comparative pharmacolinetic profiles of metoprolol and chlorthalidone administered alone or in combination to healthy volunteers. Eur J Clin Pharmacol 24: 655–660
Jordo L, Johnson A, Lundborg P et al. (1982) Bioavailability and disposition of metoprolol and hydrochlorothiazide combined in one tablet and of separate doses of hydrochlorothiazide. Br J Clin Pharmacol 14: 727–732
Nichools DP, Harron DHA et al. (1982) Comparative pharmacological and pharmacokinetic observations on propranolol and bendrofluazide administered separately and concurrently to volunteers. Br J Clin Pharmacol 14: 727–732
Roux A, Liboux A, Delhotal B, Gaillot J, Flaurat B (1983) Pharmacokinetics in man of acebutalol and hydrochlorothiazide as single agents and in combination. Eur J Clin Pharmacol 24: 801–806
Klotz U, Arant GR, Hoyumpa A, Schanker S, Wilkinson GR (1975) The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest 55: 347–359
Wan SH, Koda RJ, Naronde RF (1979) Pharmacokinetics, pharmacology of atenolol and effects of renal function. Br J Clin Pharmacol 7: 569–574
Sassard J, Pozet N, McKinsh J, Legheand J, Zech P (1973) Pharmacokinetics of atenolol in patients with renal impairment. Eur J Clin Pharmacol 12: 175
Niemeyer C, Hasenfuß A et al. (1983) Pharmacoinetics of hydrochlorothiazide in relation to renal function. Eur J Clin Pharmacol 24: 661–665
Bermann B, Croschinksy-Grind M (1979) Pharmacokinetics of hydrochlorothiazide in patients with congestive heart failure. Br J Clin Pharmacol 7: 579–583
George CF (1980) Amiloride handling in renal failure. Br J Clin Pharmacol 9: 94–95
Sunderam SG, Manikar K (1983) Hyponatraemia in the elderly. Age Ageing 12: 79–89
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Sabanathan, K., Castleden, C.M., Adam, H.K. et al. A comparative study of the pharmacokinetics and pharmacodynamics of atenolol, hydrochlorothiazide and amiloride in normal young and elderly subjects and elderly hypertensive patients. Eur J Clin Pharmacol 32, 53–60 (1987). https://doi.org/10.1007/BF00609957
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DOI: https://doi.org/10.1007/BF00609957