PHARMACOKINETICS OF BRODIMOPRIM IN SPECIAL POPULATIONS

The pharmacokinetics of brodimoprim have been investigated after singl e 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 br odimoprim bound to plasma proteins, 93%, was identical in renally impa ired patients and in healthy controls but decreased to 90% or less in liver insufficiency. The apparent distribution volume and clearance we re much higher in children than in adults. Urinary excretion of unchan ged brodimoprim amount- ed to 5-10% of the administered dose. The stea dy-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 hour s in the elderly, compared to 9% and 24% in young adults. The accumula tion factor reached 3.3 +/- 0.4 and 2.7 +/- 0.3 respectively.