Pharmacokinetics of methylprednisolone succinate, methylprednisolone, and lidocaine in the normal dog and during hemorrhagic shock.
Pharmacokinetics of methylprednisolone succinate and methylprednisolone following methylprednisolone sodium succinate administration were studied in five dogs under normal conditions and then during a severe hemorrhagic shock. In order to evaluate hepatic blood flow, lidocaine clearance was simultaneously measured. In the normal state, the clearance of methylprednisolone succinate was 1.64 +/- 0.499 L/h/kg and its half-life was 15.33 +/- 3.84 min. The systemic availability of methylprednisolone from methylprednisolone succinate was 59.9 +/- 8.3%, and the maximal methylprednisolone concentration was observed after a delay of 7.68 +/- 6.31 min. Using a reservoir technique in anesthetized dogs, severe hemorrhagic shock was obtained. Changes in lidocaine clearance indicated a subsequent reduction of hepatic blood flow. The clearance of methylprednisolone succinate decreased to 0.488 +/- 0.240 L/kg/h, and the half-life increased to 40.66 +/- 23.48 min. The exact availability of methylprednisolone from methylprednisolone succinate during shock was not calculable because methylprednisolone kinetics were time dependent. The plasma methylprednisolone concentration was relatively high and persistent during the shock. It was concluded that methylprednisolone sodium succinate is a prodrug which can be released in sufficient quantities as its active moiety (i.e., methylprednisolone) during severe hemorrhagic shock in the dog. In addition, after a single intravenous administration, the slow process of methylprednisolone elimination may give sustained methylprednisolone concentrations for several hours.
Toutain
P L
PL
INRA, Station de Pharmacologie-Toxicologie, Toulouse, France.
Autefage
A
A
Oukessou
M
M
Alvinerie
M
M
D000818:Animals; D001682:Biological Availability; D004285:Dogs; D007700:Kinetics; D008012:Lidocaine / Q000493:pharmacokinetics*; D008102:Liver Circulation; D008657:Metabolic Clearance Rate; D008775:Methylprednisolone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008776:Methylprednisolone Hemisuccinate / Q000493:pharmacokinetics*; D012771:Shock, Hemorrhagic / Q000378:metabolism*
D008776:Methylprednisolone Hemisuccinate; D008012:Lidocaine; D008775:Methylprednisolone