Summary
The absorption and disposition of metoprolol have been evaluated in 10 healthy, non-smoking, elderly individuals (mean age 73.1 years) by simultaneous determination of [3H]-metoprolol and unlabelled metoprolol. The labelled drug was given as an intravenous tracer dose, immediately followed by oral metoprolol 25 mg. The experiment was preceded by administration of metoprolol 25 mg b.i.d. for 3 days. The volume of distribution, elimination half-life and total body clearance were almost the same as previously observed in healthy, young subjects. The mean systemic availability was about 39% in the elderly, which is lower than the mean of 55% observed in a control group of young volunteers who received 50 mg b.i.d. In the elderly, the mean plasma concentration of α-OH-metoprolol was about twice as high as that of the parent drug, whereas the opposite was true of the control group. The results indicate that age-related physiological changes have a negligible effect on the pharmacokinetics of metoprolol.
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References
Landahl S, Steen B (1981) Läkemedelskonsumtion hos 70-och 75-åringar. Longitudinella data från en populationsundersökning. Läkartidningen 78 (25): 2458–2460
Lundborg P, Steen B (1976) Plasma levels and effect on heart rate and blood pressure of metoprolol after acute oral administration in twelve geriatric patients. Acta Med Scand 200: 397–402
Kendall MJ, Brown D, Yates RA (1977) Plasma metoprolol concentrations in young, old and hypertensive subjects. Br J Clin Pharmacol 4: 497–499
Castleden CM, Kaye CM, Parsons RL (1975) The effect of age on plasma levels of propranolol and practolol in man. Br J Clin Pharmacol 2: 303–306
Schneider RE, Bishop H, Yates RA, Quarterman CP, Kendall M (1980) Effect of age on plasma propranolol levels. Br J Clin Pharmacol 10: 169–170
Ishizaki T, Hirayama H, Tawara K, Nakaya H, Sato M, Sato K (1980) Pharmacokinetics and pharmacodynamics in young normal and elderly hypertensive subjects: A study using sotalol as a model drug. J Pharmacol Exp Ther 212: 173–181
Quarterman CP, Kendall MJ, Jack DB (1981) The effect of age on the pharmacokinetics of metoprolol and its metabolites. Br J Clin Pharmacol 11: 287–294
Castleden CM, George CF (1979) The effect of ageing on hepatic clearance of propranolol. Br J Clin Pharmacol 7: 49–54
Vestal RE, Wood AJJ, Shand DG (1979) Reduced β-adrenoceptor sensitivity in the elderly. Clin Pharmacol Ther 26: 181–186
Kornhauser DM, Wood AJJ, Vestal RE, Wilkinson GR, Branch RA, Shand DG (1978) Biological determinants of propranolol disposition in man. Clin Pharmacol Ther 23: 165–174
Brochner-Mortensen J (1972) A simple method for the determination og glomerular filtration rate. Scand J Clin Lab Invest 30: 271–274
Jordö L, Attman PO, Aurell M, Johansson L, Johnsson G, Regårdh CG (1980) Pharmacokinetic and pharmacodynamic properties of metoprolol in patients with impaired renal function. Clin Pharmacokinet 5: 169–180
Hoffmann K-J, Regårdh CG, Aurell M, Ervik M, Jordö L (1980) The effect of impaired renal function on the plasma levels and urinary excretion of metoprolol metabolites. Clin Pharmacokinet 5: 181–191
Regårdh CG, Jordö L, Ervik M, Lundborg P, Olsson R, Rönn O (1981) Pharmacokinetics of metoprolol in patients with hepatic cirrhosis. Clin Pharmacokinet 6: 375–388
Regårdh CG, Johnsson G, Jordö L, Lundborg P, Persson B-A, Rönn O (1980) Plasma concentrations and beta-blocking effects in normal volunteers after intravenous dose of metoprolol and propranolol. J Cardiovasc Pharmacol 2: 715–723
Ervik M, Hoffmann K-J, Kylberg-Hanssen K (1981) Selected ion monitoring of metoprolol and two metabolites in plasma and urine using deuterated internal standards. Biomed Mass Spectrom 8: 322–326
Metzler CM, Elfring L, McEwen AJ (1974) A users manual for NONLIN and associated programs. Research Biostatistics, The Upjohn Company, Kalamazoo, MI 49001
Yeh KC, Kwan KC (1978) A comparison of numerical algorithms by trapezoidal, lagrange and spline approximation. J Pharmacokinet Biopharm 6: 79–98
Vestal RE, Wood JJ, Branch RA, Shand DG, Wilkinson GR (1979) Effects of age and cigarette smoking on propranolol disposition. Clin Pharmacol Ther 26: 8–15
Regårdh CG, Borg KO, Johansson R, Johnsson G, Palmer L (1974) Pharmacokinetic studies on the selective β1-receptor antagonist metoprolol in man. J Pharmacokinet Biopharm 2: 347–364
Bond PA (1967) Metabolism of propranolol (Inderal), a potent, specific β-adrenergic receptor blocking agent. Nature 213: 721
Borg KO, Carlsson E, Hoffmann K-J, Jönsson T-E, Thorin H, Wallin B (1975) Metabolism of metoprolol-(3H) in man, the dog and the rat. Acta Pharmacol Toxicol 36[Suppl 5]: 125–135
Regårdh CG, Ek L, Hoffmann K-J (1979) Plasma levels and β-blocking effect of α-hydroxymetoprolol — metabolite of metoprolol — in the dog. Pharmacokinet Biopharm 7: 471–479
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Regårdh, C.G., Landahl, S., Larsson, M. et al. Pharmacokinetics of metoprolol and its metabolite α-OH-metoprolol in healthy, non-smoking, elderly individuals. Eur J Clin Pharmacol 24, 221–226 (1983). https://doi.org/10.1007/BF00613821
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DOI: https://doi.org/10.1007/BF00613821