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.

Amikacin (250 mg four times daily for 10 days) was administered intramuscularly to 22 patients with long-standing, severe infections of the urinary tract, in each case superimposed on chronic uropathy or nephropathy. Therapy with amikacin was completely successful in 14 patients (sterile 14-day follow-up urine specimens obtained by suprapubic needle aspiration of the bladder) and partially successful in three (sterile three-day but positive 14-day follow-up urine specimens). Five patients were judged to be treatment failures. Quantitative assessment of pyuria revealed a significant drop in the rate of excretion of white cells to near normal levels not only in patients who were cured but also in others, a finding which suggests that the infectious process had been affected by amikacin in all cases. The course of the disease in individual patients suggested that amikacin therapy can be successful after a long series of failures from treatment of such conditions with other antibiotics. Additional pharmacokinetic studies indicated that the half-life of amikacin may be increased five- to 10-fold in patients with renal insufficiency. A tentative dosage schedule was prepared for patients with various degrees of impaired renal function on the basis of average half-life values.

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