Pharmacokinetics of brodimoprim in special populations

The pharmacokinetics of brodimoprim have been investigated after single oral dose administration in children, in healthy adults, and elderly subjects, as well as in patients with mild renal failure (creatinine clearance 40-70 mL/min) or liver insufficiency (Child-Pugh grade A or B). The plasma half-life increased moderately with age. The percent brodimoprim bound to plasma proteins, 93%, was identical in renally impaired patients and in healthy controls but decreased to 90% or less in liver insufficiency. The apparent distribution volume and clearance were much higher in children than in adults. Urinary excretion of unchanged brodimoprim amounted to 5-10% of the administered dose. The steady-state pharmacokinetics of brodimoprim has also been investigated in elderly subjects (400 mg loading dose followed by 7 days 200 mg once daily). There was no significant modification of elimination half-life and of clearance upon repeated dosing. Renal excretion of brodimoprim and hydroxy metabolite at steady-state reached 9% and 14% per 24 hours in the elderly, compared to 9% and 24% in young adults. The accumulation factor reached 3.3 +/- 0.4 and 2.7 +/- 0.3 respectively.