Summary
The relationship between the plasma concentration of oxprenolol and its haemodynamic effects during physical exercise was studied in 6 healthy volunteers, in whom BP and heart rate (HR) were continuously monitored by non-invasive techniques (Fin-A-Press-Tonometer) during repeated three-minute exercise periods for 8 h after treatment. Using the fitted pharmacokinetic curve, the drug effect was related to its plasma concentration using the Emax model.
The mean EC50 for the relationship between drug concentration and heart rate during exercise (HRex) was 73.1 ng/ml, and for systolic blood pressure during exercise (SBPex) it was 112.7 ng/ml. Emax was 29.0% for HRex, and 33.2% for SBPex. There were no consistent differences between the parameters for the effects on HRex and SPBex.
Thus, using a new, non-invasive technique for continuous measurement of blood pressure, the effect of a beta-adrenoceptor blocking drug on SBPex was described with similar accuracy as its effect on HRex.
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References
McDevitt DG (1979) Adrenoceptor blocking drugs, clinical pharmacology and therapeutic use. Drugs 17: 267–288
Millar Craig MW, Mann S, Balasubramanian V, Cashman P, Raftery EB (1981) Effects of oxprenolol on the intra-arterial blood pressure response to dynamic exercise in hypertensive men. J Cardiovasc Pharmacol 3: 468–476
Johansson SR, McCall M, Wilhemsson C, Vedin JA (1980) Duration of action of beta-blockers. Clin Pharmacol Ther 27: 593–601
Gugler R, Krist R, Raczinski H, Hoffgen K, Bodem G (1980) Comparative pharmacodynamics and plasma levels of beta-adrenoceptor blocking drugs. Br J Clin Pharmacol 10: 337–343
Maury M, Berdaus B, Kehr A, Dubraze P, Giudicelli JF (1985) Comparative beta-adrenoceptor blocking effect and pharmacokinetics of bucindolol and propranolol in man. Eur J Clin Pharmacol 27: 649–652
Platzer R, Galeazzi R, Niederberger W, Rosenthaler J (1984) Simultaneous modeling of bopindolol kinetics and dynamics. Clin Pharmacol Ther 36: 5–13
Ishizaki T, Hirayama H, Taware K, Nakaya H, Sato M, Sato K (1980) Pharmacokinetics and pharmacodynamics in young normal and elderly hypertensive patients: A study using sotalol as a model drug. J Pharmacol Exp Ther 212: 173–181
McDevitt DG, Shand DG (1975) Plasma concentrations and the time-course of beta-blockade due to propranolol. Clin Pharmacol Ther 18: 708–713
Galeazzi R, Pirocino M, Weidmann P (1983) Constant kinetics and constant concentration-effect relationship during long-term beta-blockade with pindolol. Clin Pharmacol Ther 33: 733–740
Vukovich RA, Foley JE, Brown B, Willard DA, Buckley M, O'Kelley O, Fitzgerald D, Tormey W, Daragh A (1979) Effect of beta-blockers on exercise double product (systolic blood pressure×heart rate). Br J Clin Pharmacol 7: 167s-172s
Molhoek GP, Wesseling KH, Settels JJM, Van Vollenhoven E, Weeda HWH, De Wit B, Arntzenius AC (1984) Evaluation of the Penaz servo-plethysmomanometer for the continuous, non-invasive measurement of finger blood pressure. Basic Res Cardiol 79: 598–609
Smith NT, Wesseling KH, De Wit B (1985) Evaluation of two prototype devices producing noninvasive, pulsatile, calibrated blood pressure measurement from a finger. J Clin Monit 1: 17–29
Wesseling KH, Settels JJM, Van der Hoeven GMA, Nijboer JA, Butijn MWT, Dorlas JC (1985) Effects of peripheral vasoconstriction on the measurement of blood pressure in a finger. Cardiovasc Res 19: 139–145
Kendall MJ, John VA (1983) Oxprenolol: Clinical pharmacology, pharmacokinetics and pharmacodynamics. Am J Cardiol 52: 27D-33D
Bobik A, Jennings G, Korner PI, Ashley P, Jackmann G (1979) Absorption and excretion of rapid- and slow-release oxprenolol and their effects on heart rate and blood pressure during exercise. Br J Clin Pharmacol 7: 545–549
Jennings G, Bobik A, Korner P (1981) Influence of intrinsic sympaticomimetic activity of beta-adrenoceptor blockers on the heart rate and blood pressure responses to graded exercise. Br J Clin Pharmacol 12: 355–362
Brunner L, Imhof P, Jack D (1975) Relation between plasma concentrations and cardiovascular effects of oral oxprenolol in man. Eur J Clin Pharmacol 8: 3–9
Kramer B, Olshauser K, Von Hausen K, Schwanz F, Henrichs K, Mauer W, Kubler W (1981) Unterschiedliche Auswirkungen einer akuten B-blockade auf Herzfrequenz und Blutdruck bei ergometrischen Belastung. Verhandlungen der Deutschen Gesellschaft für Innere Medizin. 87. Kongress, 522–525
Racine-Poon A, Moppert J (1985) Concentration-effect relationship of oxprenolol in healthy volunteers: A retrospective analysis. Br J Clin Pharmacol 19: 143s-149s
Saunders L, Ingram D, Warrington SJ (1985) The pharmacokinetics and dynamics of oxprenolol: A simulation study with six subjects. J Pharm Pharmacol 37: 802–806
Holford NG, Sheiner LB (1981) Understanding the dose-effect relationship: Clinical application of pharmacokinetic-pharmacodynamic models. Clin Pharmacokinet 6: 429–453
Jonkers RE, Oosterhuis B, van Boxtel CJ (1987) Beta2-adrenoceptor mediated hypokalemia and its abolishment by oxprenolol. Clin Pharmacol Ther
Ishizaki T, Ohmshi A, Saski T, Chiba K, Suganuma T, Kuskisa K (1983) Concentration-effect and time-effect relationships of carteolol. Eur J Clin Pharmacol 25: 749–757
Metzler CM, Elfring GL, McEven AJ (1974) A Ser's manual for Nonlin and associated programs. Research Biostatistics, The Upjohn Company, Kalamazoo, MI
Gibaldi M, Perrier D (1975) Pharmacokinetics. Marcel Dekker, New York
Yamaoka KH, Nakagawa T, Uno T (1978) Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm 6: 165–175
McDevitt DG (1983) Beta-adrenergic blocking drugs and partial agonist activity, is it clinically relevant. Drugs 25: 331–338
Davidson C, Thadini U, Taylor SH, Hess H, Ries W (1976) Pharmacological studies with slow-release formulations of oxprenolol in man. Eur J Clin Pharmacol 10: 189–195
Vandenburg MJ, Conlon C, Ledingham JM (1981) A comparison of the effects of propranolol and oxprenolol on forearm blood flow and skin temperature. Br J Clin Pharmacol 11: 485–490
Wellstein A, Pitschner HF, Belz GG (1985) Receptor binding of propranolol is the missing link between plasma concentrations kinetics and the effect-time course in man. Eur J Clin Pharmacol 29: 131–147
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Koopmans, R., Oosterhuis, B., Karemaker, J.M. et al. Pharmacokinetic-pharmacodynamic modelling of oxprenolol in man using continuous non-invasive blood pressure monitoring. Eur J Clin Pharmacol 34, 395–400 (1988). https://doi.org/10.1007/BF00542442
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DOI: https://doi.org/10.1007/BF00542442