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The effect of oxprenolol dosage time on its pharmacokinetics and haemodynamic effects during exercise in man

European Journal of Clinical Pharmacology volume 44, pages 171–176 (1993)Cite this article

Summary

We have studied the effect of dosage time of oxprenolol (Trasicor®) on its pharmacokinetics and pharmacodynamics in six healthy volunteers. The drug effects measured were heart rate and systolic blood pressure during exercise. Oxprenolol was taken orally at 08.00 h, 14.00 h, 20.00 h, and 02.00 h in randomized order, with 1 week between successive doses.

There were differences in the pharmacokinetics of oxprenolol for the ratio between the apparent volume of distribution and systemic availability (P=0.04) and for elimination half-life (P=0.006). Both were lowest after administration at 14.00 h (163 (77) l and 1.2 (0.6) h; mean (SD)) and highest after administration at 02.00 h (229 (100) l, and 1.7 (0.6) h).

The systolic blood pressure during exercise before oxprenolol did not vary with dosage time, but heart rate during exercise before intake was lowest before dosage time 08.00 h and highest before dosage time 20.00 h (P=0.03).

The time-course of heart rate during exercise after oxprenolol was described by a model that incorporated the factors drug concentration and spontaneous diurnal variation. EC50 and Emax did not vary between dosage times. The spontaneous diurnal variation in heart rate during exercise was unaffected by oxprenolol, leading to an apparently greater effect of oxprenolol during the night than during the day.

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References

  1. Zuming L, Limin S, Chang Leng H (1986) Circadian rhythms of the onset of cerebral hemorrhage in patients. J West China Univ Med Sci 17: 290–293

    Google Scholar 

  2. Imhof PR, Muller P, Fasnacht D (1986) Observations on the circadian distribution of anginal attacks in patients with chronic, stable angina pectoris. Schweiz Rundschau Med (Praxis) 75: 1500–1503

    Google Scholar 

  3. Muller JE, Stone PH, Turi ZG (1985) Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med 313: 1315–1322

    Google Scholar 

  4. Muller JE, Ludmer PL, Willich SN, Tofler GH, Aylmer G, Klangos I, Stone PH (1987) Circadian variation in the frequency of sudden cardiac death. Circulation 75: 131–138

    Google Scholar 

  5. Rocco MB, Nabel EG, Selweyn AP (1987) Circadian rhythms and coronary artery disease. Am J Cardiol 59: 13c-17c

    Google Scholar 

  6. Millar Craig MW, Bishop CN, Raftery EB (1987) Circadian variation of blood pressure. Lancet I: 795–797

    Google Scholar 

  7. Mann S, Millar Craig MW, Melville DI, Balasubramanian V, Raftery BE (1979) Physical activity and the circadian rhythm of blood pressure. Clin Sci 57: 291–294

    Google Scholar 

  8. Richards AM, Nichols MG, Espiner EA (1986) Diurnal patterns of blood pressure, heart rate and vasoactive hormones in normal man. Clin Exp Theory Pract A8: 153–166

    Google Scholar 

  9. Mann S, Millar Craig MW, Balasubramanian V, Raftery EB (1980) Propranolol LA and ambulatory blood pressure. Br J Clin Pharmacol 10: 443–447

    Google Scholar 

  10. Mann S, Millar Craig MW, Balasubramanian V, Raftery EB (1981) Once daily beta-adrenoceptor blockade in hypertension: an ambulatory assessment. Br J Clin Pharmacol 12: 223–228

    Google Scholar 

  11. Raftery EB (1983) The effects of beta-blocker therapy on diurnal variation of blood pressure. Eur Heart J 4: 61–64

    Google Scholar 

  12. Millar Craig MW, Mann S, Balasubramanian V, Altman DG, Raftery EB (1983) The effects of oxprenolol on ambulatory intra-arterial blood pressure in essential hypertension. Eur J Clin Pharmacol 24: 713–721

    Google Scholar 

  13. Davies CTM, Sargeant AJ (1975) Circadian variation in physiological responses to exercise on a stationary bicycle ergometer. Br J Indust Med 32: 110–114

    Google Scholar 

  14. Cable NT, Reilly T (1987) Influence of circadian rhythms on arm exercise. J Hum Movement Stud 13: 13–27

    Google Scholar 

  15. Ilmarinen J, Rutenfranz J, Kylian H, Klinst F (1975) Study of the circadian variation of different circulatory and respiratory functions at submaximal and maximal ergometer work. Eur J Appl Physiol 34: 255–267

    Google Scholar 

  16. Koopmans R, Oosterhuis B, Karemaker JM, Wemer J, van Boxtel CJ (1988) Pharmacokinetic-pharmacodynamic modelling of oxprenolol in man using continuous non-invasive blood pressure monitoring. Eur J Clin Pharmacol 34: 395–400

    Google Scholar 

  17. Langner B, Lemmer B (1988) Circadian changes in the pharmacokinetics and cardiovascular effects of oral propranolol in healthy subjects. Eur J Clin Pharmacol 1988: 619–624

    Google Scholar 

  18. Jonkers RE, van Boxtel CJ, Oosterhuis B (1987) Beta-2-adrenoceptor mediated hypocalemia and its abolishment by oxprenolol. Clin Pharmacol Ther 42: 627–633

    Google Scholar 

  19. 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

    Google Scholar 

  20. Metzler CM, Elfring GL, McEven AJ (1974) A user's manual for NONLIN, and associated programs. Research biostatistics. Upjohn, Kalamazoo, MI

    Google Scholar 

  21. Gibaldi M, and Perrier D (1982) Pharmacokinetics. Dekker, New York

    Google Scholar 

  22. Dixon WJ (1983) BMDP statistical software. Univ of Cal Press, Berkeley

    Google Scholar 

  23. 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-Schmiedeberg's Arch Pharmacol 330: 42–49

    Google Scholar 

  24. 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

    Google Scholar 

  25. Melander A, McLean A (1983) Influence of food on presystemic clearance of drugs. Clin Pharmacokin 8: 286–296

    Google Scholar 

  26. Lemmer B, Nold G (1991) Circadian changes in estimated hepatic blood flow in healthy subjects. Br J Clin Pharmacol 32: 627–29

    Google Scholar 

  27. Martin BJ, Bender PR, Chen H (1986) Stress hormonal response to exercise after sleeploss. Eur J Appl Physiol 55: 210–214

    Google Scholar 

  28. Bond V, Balkissoon B, Franks BD, Brwlow R, Caprarola M, Bartley D, Banks M (1986) Effects of sleep deprivation on performance during submaximal and maximal exercise. J Sports Med 26: 169–174

    Google Scholar 

  29. Hossmann V, Fitzgerald GA, Dollery CT (1980) Circadian rhythm of baroflex reactivity and adrenergic vascular response. Cardiovasc Res 14: 125–129

    Google Scholar 

  30. Panza JA, Epstein SE, Quyyumi AA (1991) Circadian variation in vascular tone and its relation to alpha-sympathetic vasoconstrictor activity. N Engl J Med 325: 986–90

    Google Scholar 

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Affiliations

  1. Clinical Pharmacology Section, Departments of Medicine and Pharmacology, Academic Medical Centre, Amsterdam, The Netherlands

    R. Koopmans, B. Oosterhuis, J. Wemer & C. J. van Boxtel

  2. Department of Physiology, University of Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands

    J. M. Karemaker

Authors
  1. R. Koopmans
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  2. B. Oosterhuis
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  3. J. M. Karemaker
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  4. J. Wemer
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  5. C. J. van Boxtel
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Koopmans, R., Oosterhuis, B., Karemaker, J.M. et al. The effect of oxprenolol dosage time on its pharmacokinetics and haemodynamic effects during exercise in man. Eur J Clin Pharmacol 44, 171–176 (1993). https://doi.org/10.1007/BF00315476

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  • DOI: https://doi.org/10.1007/BF00315476

Key words

  • Oxprenolol
  • β-adrenoceptor blockade
  • circadian rhythm
  • haemodynamics
  • pharmacokinetics
  • exercise
  • healthy volunteers
  • kinetic-dynamic model