Chloramphenicol Pharmacokinetics in Hospitalized Patients

Abstract

The apparent body clearance of chloramphenicol was investigated in 21 hospitalized adult patients on 27 occasions. Apparent body clearance was found to be significantly lower (1.99 ± 1.49 ml/min per kg) in patients with total serum bilirubin concentrations of >1.5 mg/100 ml than in patients with serum bilirubin concentrations of ≤1.5 mg/100 ml (3.57 ± 1.72 ml/min per kg; P < 0.001). Serum protein binding of chloramphenicol was lower in cirrhotic patients (42.2 ± 6.8% bound) than in normal adults (53.1 ± 5.2% bound; P < 0.001). Low binding of chloramphenicol was also found in the serum of premature neonates (32.4 ± 8.2% bound; P < 0.001). Reduced binding in neonates implies the need for a lower therapeutic range of total chloramphenicol concentration (3.5 to 13.9 μg/ml) compared with the usual adult range (5 to 20 μg/ml). Finally, three case reports are presented which demonstrate marked abnormalities and intrasubject variation in chloramphenicol clearance.