Pharmacokinetics of intravenous chloramphenicol sodium succinate in adult patients with normal renal and hepatic function

Abstract

The pharmacokinetics of chloramphenicol (CAP) and total chloramphenicol succinate (CAPS) were studied in eight hospitalized adult patients with normal renal and hepatic function receiving intravenous chloramphenicol sodium succinate therapy. The steady-state peak concentrations of CAP (8.4-26.0 micrograms/ml) occurred at an average of 18.0 min (range 5.4-40.2) after cessation of the chloramphenicol sodium succinate infusion. Unhydrolyzed CAPS prodrug, representing 26.0 +/- 7.0% of the dose, was recovered unchanged in the urine indicating that the bioavailability of CAP from a dose of intravenous chloramphenicol succinate is not complete. A pharmacokinetic model was developed for simultaneous fitting of CAP and CAPS plasma concentration data. Pharmacokinetic parameters determined by simultaneous fitting were: V, 0.81 +/- 0.18 liters/kg; t1/2, 3.20 +/- 1.02 hr; CLB, 3.21 +/- 1.27 ml/min/kg for chloramphenicol; and V, 0.38 +/- 0.13 liters/kg; t1/2, 0.57 +/- 0.12 hr; CLB, 7.72 +/- 1.87 ml/min/kg for total chloramphenicol succinate.