Pharmacokinetics of Bisoprolol During Repeated Oral Administration to Healthy Volunteers and Patients with Kidney or Liver Disease

Summary

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 CL_CR = 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 (CL_CR < 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.