Pharmacokinetics of Chloramphenicol and Chloramphenicol Glucuronide in Horses Following Administration Per Rectum or via Nasogastric Intubation

Chloramphenicol is a broad-spectrum antibiotic used in equine practice. It is known to produce adverse effects of hyporexia/anorexia after oral administration. Administration per rectum (PR) could mitigate the appetite suppression seen with oral administration and allow its use in horses unable to receive oral medications. The objectives of this study were to evaluate the relative bioavailability of chloramphenicol administered PR or via nasogastric tube (NGT) and determine relevant pharmacokinetic/pharmacodynamic parameters and metabolic ratios. Ten healthy, adult horses were administered chloramphenicol tablets (50 mg/kg) PR or via NGT in a randomized crossover design with a washout period. Blood samples were collected at predetermined times over 24 h, and plasma concentrations of chloramphenicol and its inactive metabolite chloramphenicol glucuronide were analyzed using a validated UPLC-MS/MS assay. Chloramphenicol tablets dissolved in water were rapidly metabolized to chloramphenicol glucuronide following both routes. Maximum concentrations for PR and NGT administration were (C _max; μg/mL) 0.119 ± 0.135 and 11.7 ± 5.8, respectively. Administration PR resulted in a relative bioavailability of 0.56% ± 0.86%. The metabolic ratio of chloramphenicol glucuronide to chloramphenicol was 20.2 ± 6.19 for PR and 5 ± 1.88 for NGT. Administration of chloramphenicol PR does not reach therapeutic concentrations nor prevent significant metabolism of chloramphenicol. After administration by NGT, plasma concentrations of chloramphenicol exceeded 2 μg/mL for 3.93 ± 0.44 h.