Variability of ceftriaxone pharmacokinetics in hospitalized patients with severe infections

The pharmacokinetic behavior of ceftriaxone was studied in 60 patients with severe community- or hospital-acquired infections. Serum concentrations one to three hours after a 30-minute intravenous infusion appeared to be dose related. The mean two-hour levels were 110, 138, and 146 mg/liter, and trough values averaged 54.9, 28.5, and 16.1 mg/liter after doses of 1.0, 2.0, and 3.0 g, respectively. At 24 hours, values were at least 10 mg/liter in all but seven patients. The serum half-life of ceftriaxone in all patients and for all dosage regimens varied from 3.5 to 59.4 hours. In patients with normal renal function (serum creatinine 1.30 mg/dl or less) the mean half-life was 8.2 hours. In patients with moderate (creatinine 1.34 to 1.83 mg/dl) and severe (creatinine 2.40 mg/dl or greater) renal insufficiency, the mean serum half-lives were 12.8 and 12.4 hours, respectively. In six patients who had severe renal failure and concomitant hepatic dysfunction, half-lives ranged from 23.7 to 59.4 hours. Single daily doses of 2.0 g of ceftriaxone produced adequate serum concentrations. Dose reductions are recommended in patients with both renal and hepatic dysfunction.