Summary
Repeated doses of a new β-adrenoceptor blocking agent, befunolol, were administered orally to adult male volunteers for a cross-over comparison with propranolol. The β-adrenoceptor blocking activity of befunolol was greater than that of propranolol when assessed by the percentage reduction in exercise-induced tachycardia. The elimination half-life of drug was significantly prolonged on repeated administration of propranolol, but not of befunolol. The percentage reduction in exercise-induced tachycardia was highly correlated with the log plasma level of each drug. Both drugs produced a significant reduction in pre-exercise systolic and diastolic blood pressure, and significant attenuation of exercise-induced rise in systolic blood pressure.
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Kitagawa H, Sakai Y, Matsumura Y, Kojima H, Ofuji T (1979) Absorption, distribution and excretion of a β-adrenergic blocker, befunolol hydrochloride, in rats. Oyo Yakuri 17: 383–391
Kitagawa H, Sakai Y, Matsumura Y, Kojima H, Ofuji T (1979) Absorption, distribution and excretion of a β-adrenergic blocker, befunolol hydrochloride, at high doses and repeated administration in rats. Oyo Yakuri 17: 393–401
Kitagawa H, Sakai Y, Matsumura Y, Kojima H, Matsuda Y, Tohno M, Ofuji T (1979) Metabolism of befunolol in rats and rabbits. Oyo Yakuri 18: 889–902
Takenaka F, Ishihara T, Maruyama Y, Masumoto S, Inoue H, Okumura M, Honma H (1974) Effects of 2-acetyl-7-(2-hydroxy-3-isopropylamino)propoxy benzofuran hydrochloride, new beta-blocking agent on cardiovascular system. Folia Pharmacol Japon 70: 385–397
Masumoto S, Nakagawa T, Kudo M, Okumura M, Ukai K, Nozu K, Maruyama Y (1979) The general pharmacological studies of befunolol hydrochloride, [2-acetyl-7-(2-hydroxy-3-isopropylaminopropoxy) benzofuran hydrochloride BFE 60], a new β-adrenergic blocking agent. Iyakuhin Kenkyu 10: 741–782
Kawahara K, Ofuji T (1979) Simultaneous determination of befunolol, a β-blocking agent, and its metabolite in human plasma by gas chromatography with electron-capture detection. J Chromatogr 168: 266–272
Ofuji T, Kawahara K, Matsuda T, Uda K, Koutani Y (1979) Studies on stability and fate of befunolol in blood of mouse, rat, guinea-pig, rabbit, dog, monkey and human. Oyo Yakuri 18: 1055–1062
Tohno M, Kimura K, Nagahara M, Sakai Y, Ofuji T, Nadai T (1979) Identification of urinary metabolites of befunolol in dog and man principally by mass spectrometry. Yakugaku Zasshi 99: 944–957
Kawashima K, Levy A, Spector S (1976) Stereospecific radioimmunoassay for propranolol isomers. J Pharmacol Exp Ther 196: 517–523
Berman M, Shahn E, Weiss MF (1962) The routine fitting of kinetic data to models: A mathematical formalism for digital computers. Biophys J 2: 275–287
Evans GH, Shand DG (1973) Disposition of propranolol. V. Drug accumulation and steady-state concentrations during chronic oral administration in man. Clin Pharmacol Ther 14: 487–493
Prichard BNC, Gillam PMS (1969) Treatment of hypertension with propranolol. Br Med J 1: 7–16
Shand DG, Nuckolls EM, Oates JA (1970) Plasma propranolol levels in adults with observations in four children. Clin Pharmacol Ther 11: 112–120
Chidsey CA, Morselli P, Bianchetti G, Morganti A, Leonetti G, Zanchetti A (1975) Studies of the absorption and removal of propranolol in hypertensive patients during therapy. Circulation 52: 313–318
Evans GH, Shand DG (1973) The disposition of propranolol. VI. Independent variation in steady state circulating drug concentration and half-life as a result of plasma drug binding in man. Clin Pharmacol Ther 14: 494–500
van den Brink G, Boer P, van Asten P, Dorhoutmees EJ, Geyskes GG (1980) One and three doses of propranolol a day in hypertension. Clin Pharmacol Ther 27: 9–15
Paterson JW, Conolly ME, Dollery CT, Hayes A, Cooper RG (1970) The pharmacodynamics and metabolism of propranolol in man. Pharmacol Clin 2: 127–133
Malle T, Gaffney TE (1972) Propranolol metabolism in man and dog, mass spectrometric identification of six metabolites. J Pharmacol Exp Ther 182: 83–92
Tohno M, Kajikawa N, Yamamoto T, Ofuji T (1980) In vitro studies on species differences in befunolol-metabolizing activities. Yakugaku Zasshi 100: 933–940
Fitzgerald JD, O'Donnell SR (1971) Pharmacology of 4-hydroxypropranolol, a metabolite of propranolol. Br J Pharmacol 43: 222–235
Masumoto S, Inoue H, Maruyama Y (1979) The β-adrenergic blocking and antiarrhythmic activities of metabolites of befunolol hydrochloride. Folia Pharmacol Japon 75: 517–525
Walle T, Conradi EC, Walle UK, Fagan TC, Gaffney TE (1980) 4-Hydroxypropranolol and its glucuronide after single and longterm doses of propranolol. Clin Pharmacol Ther 27: 22–31
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Ebihara, A., Tawara, K., Oka, T. et al. Clinical pharmacology of a new β-adrenoceptor blocking drug, befunolol. Eur J Clin Pharmacol 23, 189–195 (1982). https://doi.org/10.1007/BF00547552
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DOI: https://doi.org/10.1007/BF00547552