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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 mug/ml) compared with the usual adult range (5 to 20 mug/ml). Finally, three case reports are presented which demonstrate marked abnormalities and intrasubject variation in chloramphenicol clearance.