Pharmacokinetics of indomethacin octyl ester (prodrug) and indomethacin produced from the prodrug.
A prodrug of indomethacin, indomethacin octyl ester (IM-OE), was synthesized and its pharmacokinetics was investigated in rat. To describe the time course of the plasma indomethacin and IM-OE after intravenous (iv) and oral administrations, a pharmacokinetic model with four compartments was developed. Indomethacin rapidly appeared in plasma after iv administration of IM-OE and declined in a monoexponential manner, with a rapid decline and low plasma levels of IM-OE. The plasma concentrations of indomethacin after oral administration of IM-OE were much lower than those after oral administration of indomethacin. The high concentrations of IM-OE compared with indomethacin were detected in liver 3 h after oral dosing of the prodrug, although IM-OE was not detected in plasma. A good fit was obtained between the observed and calculated curves based on the model, which includes a conversion rate constant of IM-OE to indomethacin for both iv and oral dosings of IM-OE. Additionally, the model could successfully describe the plasma concentration versus time profiles after indomethacin dosings.
Ogiso
T
T
Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.
Iwaki
M
M
Kinoshita
T
T
Tanino
T
T
Paku
T
T
D000284:Administration, Oral; D000818:Animals; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
D011355:Prodrugs; D007213:Indomethacin