In recent years there has been a renewal of interest in chloramphenicol, predominantly because of the emergence of ampicillin-resistantHaemophilus influenzae,the leading cause of bacterial meningitis in infants and children. Three preparations of chloramphenicol are most commonly used in clinical practice: a crystalline powder for oral administration, a palmitate ester for oral administration as a suspension, and a succinate ester for parenteral administration. Both esters are inactive, requiring hydrolysis to chloramphenicol for antibacterial activity. The palmitate ester is hydrolysed in the small intestine to active chloramphenicol prior to absorption. Chloramphenicol succinate acts as a prodrug, being converted to active chloramphenicol while it is circulating in the body.Various assays have been developed to determine the concentration of chloramphenicol in biological fluids. Of these, high-performance liquid chromatographic and radioenzymatic assays are accurate, precise, specific, and have excellent sensitivities for chloramphenicol. They are rapid and have made therapeutic drug monitoring practical for chloramphenicol.The bioavailability of oral crystalline chloramphenicol and chloramphenicol palmitate is approximately 80%. The time for peak plasma concentrations is dependent on particle size and correlates within vitrodissolution and deaggregation rates. The bioavailability of chloramphenicol after intravenous administration of the succinate ester averages approximately 70%, but the range is quite variable. Incomplete bioavailability is the result of renal excretion of unchanged chloramphenicol succinate prior to it being hydrolysed to active chloramphenicol. Plasma protein binding of chloramphenicol is approximately 60% in healthy adults. The drug is extensively distributed to many tissues and body fluids, including cerebrospinal fluid and breast milk, and it crosses the placenta. Reported mean values for the apparent volume of distribution range from 0.6 to 1.0 L/kg. Most of a chloramphenicol dose is metabolised by the liver to inactive products, the chief metabolite being a glucuronide conjugate; only 5 to 15% of chloramphenicol is excreted unchanged in the urine. The elimination half-life is approximately 4 hours. Inaccurate determinations of the pharmacokinetic parameters may result by incorrectly assuming rapid and complete hydrolysis of chloramphenicol succinate.The pharmacokinetics of chloramphenicol succinate have been described by a 2-compartment model. The reported values for the apparent volume of distribution range from 0.2 to 3.1 L/kg. Chloramphenicol succinate is metabolised (hydrolysed) by esterases in the body to active chloramphenicol. Approximately 30% of the succinate ester is excreted unchanged in the urine, with a reported range of 6 to 80%.Plasma protein binding and the clearance of chloramphenicol are reduced and the elimination half-life prolonged in patients with liver disease, but the elimination half-life is not significantly changed by renal dysfunction. Serum chloramphenicol concentrations are higher in patients with renal impairment after the administration of intravenous chloramphenicol succinate, but not oral chloramphenicol; this is due to a reduction in renal excretion of the succinate ester, resulting in increased bioavailability of active chloramphenicol. Plasma protein binding is decreased in uraemic patients, apparently due to displacement by unidentified substances. In premature and newborn infants, oral absorption of chloramphenicol after administration of the palmitate ester is slow and unreliable. The elimination of both chloramphenicol and chloramphenicol succinate is decreased in these infants as a result of immature hepatic and renal function. Plasma protein binding is also lower in newborn infants than in children and adults. The elimination of chloramphenicol may also be markedly impaired in patients in shock.Chloramphenicol impairs the metabolism of tolbutamide, chlorpropamide, cyclophosphamide, phenytoin, phenobarbitone and dicoumarol. Paracetamol (acetaminophen) has been reported to decrease the metabolism of chloramphenicol. Phenytoin and phenobarbitone hasten the elimination of chloramphenicol, most likely due to enzyme induction. Mannitol, ethacrynic acid, hydrochlorothiazide and clopamide increase the renal excretion of chloramphenicol, whereas frusemide (furosemide) decreases its renal excretion.Peak chloramphenicol concentrations of 10 to 20 &mgr;g/ml and trough concentrations of 5 to 10 &mgr;g/ml are generally desirable for most infections. Therapeutic concentrations depend on the sensitivity of the specific offending organism, in addition to the type and severity of infection. Concentration-dependent bone marrow suppression has been associated with sustained peak serum concentrations ≥ 25 &mgr;g/ml and trough concentrations ≥ 10 &mgr;g/ml. The ‘grey syndrome’ has been associated with chloramphenicol concentrations of ≥ 40 &mgr;g/ml.