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

Abstract

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 micrograms/L and 11 micrograms/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 micrograms/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 less than 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 micrograms/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.

Pharmacokinetic Variability of Routinely Administered Bisoprolol in Middle-Aged and Elderly Japanese Patients

“…: 3.0Ϯ1.0 h). 2,16) In the present study, no plasma concentration data of bisoprolol was obtained at the absorption phase (0-2.3 h after oral administration). Therefore, the one-compartment model with repetitive bolus dosing was parameterized in terms of CL/F and V/F.…”

Simulation of the pharmacokinetics of bisoprolol in healthy adults and patients with impaired renal function using whole-body physiologically based pharmacokinetic modeling

“…Therefore, pathological conditions such as renal failure may alter the exposure and disposition of bisoprolol and accordingly cause modifications in the therapeutic efficacy or side effects. These modifications might require dosage adjustment [8][9][10] . In light of this need, clinical pharmacokinetic studies of bisoprolol have been undertaken to explore and support the use of bisoprolol in patients with impaired renal function [9,10] .…”

“…These modifications might require dosage adjustment [8][9][10] . In light of this need, clinical pharmacokinetic studies of bisoprolol have been undertaken to explore and support the use of bisoprolol in patients with impaired renal function [9,10] . However, the changes of the pharmacokinetics in diverse populations were not available before the corresponding clinical studies, which is the time when an accurate approach for clinical pharmacokinetics projection is most needed.…”

“…Clinical pharmacokinetic data for both intravenous and oral administration of bisoprolol in healthy adults and patients with impaired renal function were obtained from the literature [10,[15][16][17] . The pharmacokinetic studies after intravenous administration of bisoprolol at two doses were conducted in 8 Western female subjects (age 25±3 years) [15] and 12 Western male subjects (age 37±12 years) [16] , respectively.…”

“…Mean data in the aforementioned publications were captured by computer digitization and used for development and validation of the WB-PBPK model. Plasma concentration-time profiles of bisoprolol following multiple oral administration in healthy volunteers (age 23±1 years, n=8) and patients with impaired renal function (age 59±5 years, creatinine clearance=28±5 mL/min per 1.73 m 2 , n=11) were obtained from the same source [10] .…”