title: 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.
authors.affiliation: Neonatal Screening Center, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanging 210004, P R China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.forename: Jianheng
authors.initials: J
authors.lastname: Zheng
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.forename: Jiake
authors.initials: J
authors.lastname: He
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.forename: Pengfei
authors.initials: P
authors.lastname: Song
authors.forename: Xijing
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013839:Thiamphenicol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D011355:Prodrugs; D013839:Thiamphenicol; C028813:thiamphenicol glycinate