Summary
In 6 healthy volunteers the pharmacokinetics of bisoprolol under steady-state conditions was investigated over three consecutive phases: over 7 days of 10 mg of bisoprolol once daily per os, 7 days of 10 mg of bisoprolol once daily plus 400 mg of cimetidine t.i.d. and 14 days of 10 mg of bisoprolol and 600 mg of rifampicin once daily with adequate intervals free of medication. After therapy with bisoprolol alone peak plasma levels (C ssmax ) of the beta-blocker were 55.5±6.4 ng/ml (x±SEM), area under the plasma level-time curve (AUCτ) was 597±70 ng/ml.h, total body clearance (CL) 15.8±1.8 l/h and elimination half-lives (t1/2β) 10.1±1.2 h. Cimetidine did not cause any significant changes in the pharmacokinetics of bisoprolol. Co-administration of rifampicin resulted in a decrease in C ssmax (43.0±6.9 ng/ml), AUCτ (397±54 ng/ml·h) and t1/2β (6.2±0.4 h). Accordingly, total body clearance increased to 23.8±2.51/h (p<0.05). In conclusion bisoprolol showed a statistically significant but probably clinically not important interaction with the enzyme-inducing drug rifampicin, but not with the enzyme inhibitor cimetidine.
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References
Bennett PN, John VA, Whitmarsh VB (1982) Effect of rifampicin on metoprolol and antipyrine kinetics. Br J Clin Pharmacol 13: 387–391
Brodde O-E, Daul A, Bock KD (1985) The intrinsic sympathomimetic activity of β-adrenoceptor (R) antagonists is not β-R-subtype selective. Naunyn-Schmiedebergs Arch Pharmacol 326 [Suppl]: R 81
Dorow P, Tönnesmann U (1984) Dose-response relationship of the β-adrenoceptor antagonist bisoprolol in patients with coronary heart disease and chronic obstructive bronchitis. Eur J Clin Pharmacol 27: 135–139
Feely J, Wilkinson GR, Wood AJJ (1981) Reduction of liver blood flow and propranolol metabolism by cimetidine. N Engl J Med 304: 692–695
Herman RJ, Nakamura K, Wilkinson GR, Wood AJJ (1982) Induction of propranolol metabolism in man by rifampicin. Pharmacologist 24: 181
Kirch W, Köhler H, Spahn H, Mutschler E (1981) Interaction of cimetidine with metoprolol, propranolol or atenolol. Lancet 2: 531–532
Kirch W, Spahn H, Köhler H, Ohnhaus EE, Mutschler E (1982) Interaction of metoprolol, propranolol and atenolol with concurrent administration of cimetidine. Klin Wochenschr 60: 1401–1407
Leopold G, Pabst J, Ungethüm W, Bührung KU Phase I studies on EMD 33 512, a new β1-selective adrenoceptor blocking agent. Clin Pharmacol Ther 31: 243 (Abstr B4)
Leopold G, Pabst J, Ungethüm W, Bühring W (1986) Basic pharmacokinetic profile of bisoprolol, a new high β1-selective adrenoceptor antagonist. J Clin Pharmacol (in press)
Ohnhaus EE, Heidemann H, Meiner J, Maurer G (1982) Metabolism of pindolol in patients with renal failure. Eur J Clin Pharmacol 22: 423–428
Ohnhaus EE (1983) The effect of different administration periods on the time course of enzyme induction in man. Clin Pharmacol Ther 33: 259 (Abstr II-B)
Park BK (1978) A direct radioimmunoassay 6-β-hydroxycortisol in human urine. J Steroid Biochem 2: 963–699
Schliep HJ, Harting J (1984) β1-Selectivity of bisoprolol, a new β-adrenoceptor antagonist in aneasthetized dogs and guinea pigs. J Cardiovasc Pharmacol 6: 1156–1160
Spahn H, Krich W, Mutschler E (1983) The interaction of cimetidine with metoprolol, atenolol, propranolol, pindolol and penbutolol. Br J Clin Pharmacol 15: 500–501
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Kirch, W., Rose, I., Klingmann, I. et al. Interaction of bisoprolol with cimetidine and rifampicin. Eur J Clin Pharmacol 31, 59–62 (1986). https://doi.org/10.1007/BF00870987
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DOI: https://doi.org/10.1007/BF00870987