Pharmacokinetics and bioavailability of chloramphenicol in normal and febrile goats

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Abstract
The effect of induced fever on the plasma concentrations and disposition kinetics of chloramphenicol (CHPC) was studied in adult goats. Fever was induced and maintained for 12 h by injecting Escherichia coli endotoxin (0.1 .mu.g/kg, i.v.) and repeating it at half the dose (0.05 .mu.g/kg) 8 h later. Pharmacokinetics of CHPC was studied in both normal (n = 6) and febrile (n = 6) animals following intravenous administration of CHPC Na-succinate (25 mg/kg). Intramuscular bioavailability of the drug was also investigated in both normal and febrile animals. Pharmacokinetics of CHPC following intravenous administration could be described by a two-compartment open model in both normal and febrile animals. In normal animals the half-life of CHPC was 73.0 .+-. 4.95 min and the volume of distribution was 2.217 .+-. 0.24 l/kg. These and other pharmacokinetic parameters did not differ significantly (P < 0.05) between normal and febrile animals, except for C0p and A. Absorption of CHPC following intramuscular administration was good as indicated by its high bioavailability in both normal (83.34%) and febrile (81.98%) animals. Volume of distribution is usually expected to change when the febrile state is induced. Lack of such an effect in the present study could be due to high individual variation, or to the fact that CHPC already has a relatively large volume of distribution, which is less likely to be altered by a febrile state of short duration.