Summary
The volumes of distribution of theβ-adrenoceptor blocking agents propranolol and atenolol, and the calcium antagonist verapamil, during exercise have been investigated. Changes in the plasma concentrations of atenolol and propranolol during exhaustive exercise at 70% of maximal aerobic power were compared after 1 week of oral treatment (propranolol 80 mg b. d. and atenolol 100 mg once daily) in 12 healthy volunteers. In a second study the effect of 10 min exercise at 50 % of maximal aerobic power on steady state plasma concentrations of propranolol, atenolol and verapamil was compared in 7 healthy subjects. The drugs were administered by a continuous intravenous infusion.
The plasma concentration of atenolol was not changed by exercise in either study, but the plasma concentrations of propranolol and verapamil were significantly increased in both studies. However, after correction for changes in plasma volume during exercise, the plasma propranolol concentration was not significantly elevated in the second study.
From the results it is concluded that exercise led to a reduction in the volume of distribution of propranolol during prolonged exercise (25 min) at 70 % Wmax, which was not clearly demonstrable during 10 min exercise at 50 % Wmax. The volume of distribution of verapamil was reduced during 10 min exercise at 50 % Wm, No change in the volume of distribution of atenolol during exercise could be shown. The changes in the volumes of distribution of propranolol and verapamil during exercise may contribute to preventing an increase in the half-life of these drugs in patients performing prolonged physical exercise.
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Arends BG, Böhm ROB, Van Kemenade JE, Rahn KH, Van Baak MA (1986) Influence of physical exercise on the pharmacokinetics of propranolol. Eur J Clin Pharmacol 31: 375–377
Åstrand P-O, Rodahl K (1986) Textbook of Work Physiology. McGraw-Hill, New York
Bianchetti G, Elghozi JL, Gomeni R, Meyer P, Morselli PL (1980) Kinetics of distribution of dl-propranolol in various organs and discrete brain areas of the rat. J Pharmacol Exp Ther 214: 682–687
Daniell HB, Walle T, Gaffney TE, Webb JG (1979) Stimulation-induced release of propranolol and norepinephrine from adrenergic neurons. J. Pharmacol EXP Ther 208: 354–359
Davies MK, McAinsh J (1986) Tissue atenolol levels following chronicβ-adrenoceptor blockade using oral atenolol in dogs. J Pharmaceut Pharmacol 38: 316–319
Dill DB, Costill DL (1974) Calculation of percentage changes in volume of blood, plasma, and red cells in dehydration. J Appl Physiol 37: 247–248
Goodman Gilman A, Rall TW, Nies AS, Taylor P (eds) (1990) Goodman and Gilman's. The pharmacological basis of therapeutics. Pergamon, New York
Hamann SR, Todd GD, McAllister RG (1983) The pharmacology of verapamil: V Tissue distribution of verapamil and norverapamil in rat and dog. Pharmacology 27: 1–8
Hurwitz GA, Webb JG, Walle T, Bai SA, Daniell HB, Gourley L, Boyd Loadholt C, Gaffney TE (1983) Exercise-induced increments in plasma levels of propranolol and noradrenaline. Brit J Clin Pharmacol 16: 599–608
Jorfeldt L, Juhlin-Dannfelt A, Karlsson J (1978) Lactate release in relation to tissue lactate in human skeletal muscle during exercise. J Appl Physiol 44: 350–352
Lemmer B, Winkler H, Ohm T, Fink M (1985) Chronopharmacokinetics of beta-receptor blocking drugs of different lipophilicity (propranolol, metoprolol, sotalol, atenolol) in plasma and tissues after single and multiple dosing in the rat. Naunyn-Schmied Arch Pharmacol 330: 42–49
Mooij J, Arends B, Van Kemenade J, Böhm R, Rahn KH, Van Baak MA (1986) Influence of prolonged submaximal exercise on the pharmacokinetics of verapamil in humans. J Cardiovasc Pharmacol 8: 940–942
Mooij J, Van Baak M, Böhm R, Does R, Petri H, Van Kemenade J, Rahn KH (1987) The effects of verapamil and propranolol on exercise tolerance in hypertensive patients. Clin Pharmacol Ther 41: 490–495
Pivarnik JM, Montain SJ, Graves JE, Pollock ML (1988) Alterations in plasma volume, electrolytes and protein during incremental exercise at different pedal speeds. Eur J Appl Physiol 57: 103–109
Rowell LB, Blackmon JR, Bruce RA (1964) Indocyanine green clearance and estimated hepatic blood flow during mild to maximal exercise in upright man. J Clin Invest 43: 1677–1690
Russell MP, Webb JG, Walle T, Daniell HB (1983) Adrenergic nerve stimulation-induced release of propranolol from the perfused hindlimb and spleen of the dog and associated changes in postjunctional response. J Pharmacol Exp Ther 226: 324–329
Schneck DW, Pritchard JF, Hayes AH (1977) Studies on uptake and binding of propranolol by rat tissues. J Pharmacol Exp Ther 203: 621–629
Schwartz JB, Todd E, Abernethy DR, Mitchell JR (1986) Steady state verapamil tissue distribution in the dog: differing tissue accumulation. Pharmacology 32: 307–312
Takahashi H, Ogata H, Kanno S, Takeuchi H (1990) Plasma protein binding of propranolol enantiomers as a major determinant of their stereoselective tissue distribution in rats. J Pharmacol Exp Ther 252: 272–278
Todd EL, Abernethy DR (1987) Physiological pharmacokinetics and pharmacodynamics of (±)-verapamil in female rats. Biopharmaceut Drug Dispos 8: 285–297
Van Baak MA (1990) Influence of exercise on the pharmacokinetics of drugs. Clin Pharmacokin 19: 32–43
Yata N, Toyoda T, Murakami T, Nishiura A, Higashi Y (1990) Phosphatidylserine as a determinant for the tissue distribution of weakly basic drugs in rats. Pharmaceut Res 7: 1019–1025
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van Baak, M.A., Mooij, J.M.V. & Schiffers, P.M.H. Exercise and the pharmacokinetics of propranolol, verapamil and atenolol. Eur J Clin Pharmacol 43, 547–550 (1992). https://doi.org/10.1007/BF02285100
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DOI: https://doi.org/10.1007/BF02285100