Pharmacokinetics of Bisoprolol During Repeated Oral Administration to Healthy Volunteers and Patients with Kidney or Liver Disease
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The pharmacokinetics of bisoprolol were investigated following oral administration of 10mg once daily for 7 days in 8 healthy subjects, in 14 patients with different degrees of renal impairment and in 18 patients with liver disease.
In healthy subjects peak and trough steady-state concentrations of 52 µg/L and 11 µg/ L, respectively, an elimination half-life of 10.0 hours and total body clearance of 14.2 L/ h were observed. 5.21 mg/24 hours of unchanged bisoprolol were recovered following urinary excretion during the dosage interval. In 11 patients with renal impairment (mean CLCR = 28 ± 5 ml/min/1.72m2) half-life was prolonged to 18.5 hours, and peak and trough concentrations were 74 and 32 µg/L, respectively. Correspondingly, urinary excretion decreased to 3.35 mg/24 hours and total body clearance to 7.8 L/h. In uraemic patients (CLCR < 5 ml/min/1.73m2) the total clearance of bisoprolol was 5.0 L/h and the elimination half-life was 24.2 hours. In patients with liver cirrhosis half- life increased to 13.5 hours, steady-state peak and trough concentrations increased to 62 and 22 µg/L, respectively, and total body clearance decreased to 10.8 L/h.
The present study indicates that in patients with impairment of kidney or liver function accumulation of bisoprolol above a factor of 2 did not occur. However, in the terminal stages of insufficiency of kidney or liver function bisoprolol dosage should not exceed 10mg.
KeywordsAtenolol Antipyrine Bisoprolol Total Body Clearance Uraemic Patient
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- Gibaldi M, Perrier D. Pharmacokinetics, 2nd ed. Marcel Dekker, Inc., New York 1982Google Scholar
- Leopold G, Pabst J, Ungethüm W, Bühring KU. Phase I studies on EMD 33 512, a new β1-selective adrenoceptor blocking agent. Abstract. Clinical Pharmacology and Therapeutics 31: 243, 1982Google Scholar
- Leopold G, Pabst J, Ungethüm W, Bühring W. Basic pharmacokinetics of bisoprolol, a new highly β1-selective adrenoceptor antagonist. Journal of Clinical Pharmacology, in press, 1986Google Scholar
- Sotaniemi EA. Role of liver enzyme activity in the metabolism of some beta-blocking compounds. Current Therapeutic Research 28: 45S–50S, 1980Google Scholar