The pharmacokinetics of once-daily dosing of ceftriaxone in critically illpatients

The aim of this study was to determine the pharmacokinetic profile of the n ormal recommended dose of ceftriaxone in critically ill patients and to est ablish whether the current daily dosing recommendation maintains plasma con centrations adequate for antibacterial efficacy. Ceftriaxone at a recommend ed dose of 2 g iv was administered od to 12 critically ill patients with se vere sepsis and normal serum creatinine concentrations. Blood samples were taken at predetermined intervals over the first 24 h and on day 3 for measu rement of ceftriaxone concentrations. There was wide variability in drug di sposition, explained by the presence of variable renal function and identif ied by the measurement of creatinine clearance. In nine patients with norma l renal function, there was a high level of creatinine clearance(mean +/- S .D., 41 +/- 12 mL/min) and volume of distribution (20 +/- 3.3 L), which res ulted in an elimination half-life of 6.4 +/- 1.1 h. In comparison with norm al subjects, ceftriaxone clearance was increased 100%, volume of distributi on increased 90% and the elimination half-life was similar. Three patients had substantially suboptimal plasma ceftriaxone concentrations. We confirm previous findings that ceftriaxone clearance in critically ill patients cor relates with renal clearance by glomerular filtration. The elimination half -life is prolonged (21.4 +/- 9.8 h) in critically ill patients with renal f ailure when compared with previously published data in non-critically ill p atients with renal failure. We conclude that in critically ill patients wit h normal renal function, inadequate plasma concentrations may result follow ing od bolus dosing of ceftriaxone. Drug accumulation may occur in critical ly ill patients with renal failure.