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 c1.5 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 ,ug/ml) compared with the usual adult range (5 to 20 Ag/ml). Finally, three case reports are presented which demonstrate marked abnormalities and intrasubject variation in chloramphenicol clearance.As a result of the activity of chloramphenicol (CAP) against anaerobic organisms (5) and Haemophilus influenzae which are resistant to ampicillin (2), it has gained new popularity. Use of this agent is, however, coupled with serious potential toxicities. Idiosyncratic aplastic anemia is extremely rare (25) but must be weighed as a factor in the choice of this agent. Dose-related, and thus avoidable, toxicities include normocytic bone marrow suppression, which is associated with serum concentrations exceeding 25 yig/ml and prolonged courses of therapy (13,19,25), and a syndrome consisting of cardiovascular collapse, gastrointestinal distress, respiratory depression, and coma. This symptom complex, commonly referred to as the grey syndrome, has been reported in neonates (3,12,22,24), infants (4), and adults (11, 23) and is associated with serun CAP concentrations ranging from 40 to 200 ,ug/ml.CAP is extensively metabolized. In normal adults approximately 90% of an oral dose is excreted in urine within 24 h (8). Of this quantity, only 5 to 10% is excreted as unchanged drug (7). The principal metabolite is a glucuronide which is formed in the liver and is actively secreted by the kidney (6). It is reasonable to expect decreased clearance of the drug in patients with impaired liver function. McCurdy (13) and Suhrland and Weisberger (20) reported higher CAP serum concentrations in patients with cirrhosis of the liver compared with normal t Present address:

Pharmacokinetics of anti-infectious reagents in silkworms

“…1). Data for mammals (chloramphenicol 21 and vancomycin 22 ), rabbit (tetracycline 23 ), sheep (rifampicine 24 ), rat (micafungin 25 ), and dog (fluconazole 26 ) are cited from the indicated literature.…”

Comparison of cefamandole, cephalothin, ampicillin, and chloramphenicol in experimental Escherichia coli meningitis

“…These results emphasize the potential importance of monitoring antibiotic concentrations in septic patients, particularly an agent such as chloramphenicol (7). Return of antibiotic concentrations to expected levels after infusions of 12 or 24 h may reflect improved clinical status of the animals and restoration of normal kinetics.…”

“…coli C13NK1, isolated from a neonate with meningitis, was provided for this study by George McCracken, Jr., University of Texas Health Science Center, Dallas. After overnight growth on Mueller-Hinton (MH) agar (Difco), a suspension of organisms in phosphate-buffered saline was prepared and adjusted with the help of nephelometry (Coleman 6A Spectrophotometer; Coleman Instruments, Maywood, Ill.) to a density of 7.0 x 107 to 8.0 x 107 colony-forming units (CFU)/ml. A cisternal puncture was performed with a 20-gauge needle and a 1.0-ml tuberculin syringe; 0.5 ml of CSF was withdrawn, and 0.5 ml of the bacterial suspension was injected.…”

Azithromycin and Chloramphenicol Diminish Neutrophil Extracellular Traps (NETs) Release

“…Azithromycin and chloramphenicol were purchased from Sigma-Aldrich and diluted in protein-free RPMI medium supplemented with 10 mM HEPES (ThermoFisher Scientific, Waltham, MA, USA) to give a final concentration of 0.5, 10 and 50 μg/mL (azithromycin) or 10 and 50 μg/mL (chloramphenicol) in each experiment. The concentrations used in the study for chloramphenicol are the same as its therapeutic serum concentration, which is 2–50 μg/mL [ 27 ]. For azithromycin, we used concentrations similar to those achieved in white blood cells during therapy (0–40 μg/mL; serum concentrations: up to 0.4 μg/mL) [ 28 ].…”