Abstract
The pharmacokinetics of propranolol after the administration of 40, 80, and 120 mg p.o. and 10 mg i.v. was studied in nine healthy male volunteers. Propranolol was analyzed after extraction and derivatization by gas-liquid chromatography. A multiexponential curve-stripping program was used for the pharmacokinetic analysis. The volume of distribution was about 6 liters · kg −1,bioavailability around 25%, with a mean terminal half-life of 6hr. There was no evidence of either dose dependent disposition kinetics or an oral threshold dose. A slight increase in urine volume was observed after propranolol administration.
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J. W. Paterson, M. E. Conolly, C. T. Dollery, A. Hayes, and R. G. Cooper. The pharmacodynamics and metabolism of propranolol in man.Pharmacol. Clin. 2:127–133 (1970).
D. G. Shand, E. M. Nuckolls, and J. A. Oates. Plasma propranolol levels in adult.Clin. Pharmacol. Ther. 11:112–120 (1970).
C. F. George, T. Fenyvesi, M. E. Conolly, and C. T. Dollery. Pharmacokinetics of dextro-, laevo- and racemic propranolol in man.Eur. J. Clin. Pharmacol. 4:74–76 (1972).
D. G. Shand and R. E. Rangno. The disposition of propranolol. I. Elimination during oral absorption in man.Pharmacology. 7:159–168 (1972).
G. H. Evans and D. G. Shand. Disposition of propranolol. V. Drug accumulation and steady-state concentrations during chronic oral administration in man.Clin. Pharmacol. Ther. 14:487–493 (1973).
G. H. Evans and D. G. Shand. Disposition of propranolol. VI. Independent variation in steady-state circulating drug concentrations and half-life as a result of plasma drug binding in man.Clin. Pharmacol. Ther. 14:494–500 (1973).
G. H. Evans, A. S. Nies, and D. G. Shand. The disposition of propranolol. III. Decreased half-life and volume of distribution as a result of plasma binding in man, monkey, dog and rat.J. Pharmacol. Exp. Ther. 186:114–122 (1973).
C. A. Chidsey, P. Morselli, G. Bianchetti, A. Morganti, G. Leonetti, and A. Zanchetti. Studies of the absorption and removal of propranolol in hypertensive patients during therapy.Circulation 52:313–318 (1975).
R. Gomeni, G. Bianchetti, R. Sega, and P. L. Morselli. Pharmacokinetics of propranolol in normal healthy volunteers.J. Pharmacokin. Biopharm. 5:183–192 (1977).
A. J. J. Wood, R. E. Vestal, G. R. Wilkinson, and D. G. Shand. Comparison of the bioavailability of propranolol during single and chronic oral dosing.Clin. Pharmacol. Ther. 23:137–370 (1978).
Y. A. Weiss, M. E. Safar, C. Chevillard, A. Frydman, A. Simon, P. Lemaire, and J. M. Alexandre. Comparison of the pharmacokinetics of intravenous DL-propranolol in borderline and permanent hypertension.Eur. J. Clin. Pharmacol. 10:387–393 (1976).
A. S. Nies and D. G. Shand. Clinical pharmacology of propranolol.Circulation 52:6–15 (1975).
R. Davies, A. Morganti, P. Morselli, T. Pickering, G. Bianchetti, J. Romankiewicz, and J. Laragh. Beta-blockade and blood-levels after low-dose oral propranolol: the hepatic “first-pass” threshold revisited.Lancet 1:407–410 (1978).
L. Borgström, C. G. Johansson, H. Larsson, and R. Lenander. Pharmacokinetics of bendroflumethiazide after low oral doses.J. Pharmacokin. Biopharm. 9:431–441 (1981), this issue.
R. H. Gotham and D. Shand. Spuriously low plasma propranolol concentrations resulting from blood collection methods.Clin. Pharmacol. Ther. 18:535–538 (1975).
E. Di Salle, K. M. Baker, S. R. Bareggi, W. D. Watkins, C. A. Chidsey, A. Frigerio, and P. M. Marselli. A sensitive gas chromatographie method for the determination of propanolol in human plasma.J. Chromatogr. 84:347–353 (1973).
T. Walle. GLC determination of propranolol, other β-blocking drugs, and metabolites in biological fluids and tissues.J. Pharm. Sci. 63:12:1885–1891 (1974).
C. M. Metzler. A users manual for NONLIN. The Upjohn Company Technical Report 7292/69/7292/005, Kalamazoo, Mich., 1969.
A. J. Sedman and J. G. Wagner. AUTOAN, a decision-making pharmacokinetic computer program. Publication Distribution Service, Ann Arbor, Mich., 1974.
A. Hayes and R. G. Cooper. Studies on the absorption, distribution and excretion of propranolol in rat, dog and monkey.J. Pharmacol. Exp. Ther. 176:302–311 (1971).
R. C. Tarazi, E. D. Frohlich, and H. P. Duston. Plasma volume changes with long-term beta-adrenergic blockade.Am. Heart J. 82:770–776 (1971).
J. L. Imbs, M. O. Spach, M. Schmidt, and J. Schwartz. Effet du propranolol sur la concentration des urines.Thérapie. 32:329–335 (1977).
A. Westerlund and L. Hansson. Once daily treatment of hypertension.Br. Med. J. 2:877 (1976).
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Borgström, L., Johansson, CG., Larsson, H. et al. Pharmacokinetics of propranolol. Journal of Pharmacokinetics and Biopharmaceutics 9, 419–429 (1981). https://doi.org/10.1007/BF01060886
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DOI: https://doi.org/10.1007/BF01060886