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

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.

Keywords::

• Pharmacokinetics
• thiamphenicol glycinate
• thiamphenicol
• beagle dog
• prodrug