Pharmacokinetics of the prodrug thiamphenicol glycinate and its active parent compound thiamphenicol in beagle dogs following intravenous administration

Xenobiotica. 2011 Mar;41(3):226-31. doi: 10.3109/00498254.2010.535218. Epub 2010 Nov 23.

Abstract

1. This study investigated the pharmacokinetics of thiamphenicol glycinate (TG) and thiamphenicol (TAP) in beagles (n = 6) after intravenous administration of 50 mg/kg TG hydrochloride. Plasma concentrations of TG and TAP were measured by a HPLC-UV method. 2. Two-compartment model was selected to describe the pharmacokinetic characteristics of TG and TAP in vivo. Main parameters were as follows: AUC(0-∞) of TAP and TG were 16,328 ± 1682 µg·min/mL and 3943 ± 546 µg·min/mL, respectively. The total plasma clearance (CL) of TG and TAP were 12.7 ± 2.0 mL/min/kg and 2.5 ± 0.3 mL/min/kg, respectively. Mean residence time (MRT) of TG and TAP were 27.5 ± 3.5 and 207.2 ± 20.2 min, respectively. The transformative rate constant (k(1M)) from TG to TAP was 0.0477 ± 0.0028 min(-1). The elimination rate constant (k(M10)) from TAP was 0.0238 ± 0.0044 min(-1). Coefficients of variation (CV) between observed values and predicted ones were 5.9% and 18.2%, respectively. The volume of distribution of the central compartment for TG (V(C)) and TAP (V(CM)) were 0.264 ± 0.022 L/kg and 0.127 ± 0.023 L/kg, respectively. 3. Pharmacokinetic parameters suggested that TG was presumably cleaved quickly by tissue esterase to release TAP for effectiveness in beagles after administration.

MeSH terms

  • Animals
  • Dogs
  • Female
  • Injections, Intravenous
  • Male
  • Prodrugs / administration & dosage
  • Prodrugs / pharmacokinetics*
  • Thiamphenicol / administration & dosage
  • Thiamphenicol / analogs & derivatives*
  • Thiamphenicol / blood
  • Thiamphenicol / pharmacokinetics*

Substances

  • Prodrugs
  • Thiamphenicol
  • thiamphenicol glycinate