Pharmacokinetics of methylprednisolone during acute renal allograft rejection.
High dose methylprednisolone is administered empirically by fixed daily boluses to renal transplant recipients who are experiencing acute rejection episodes. Little information is available characterizing the pharmacokinetics of high-dose methylprednisolone in these individuals, who are often acutely ill. Therefore, 5 renal transplant recipients (2 men; 3 women) were studied during an acute rejection episode (mean serum creatinine = 2.6 +/- 0.7 mg/dl) which occurred within the first 8 months post-transplantation. The rejection episode was characterized clinically by at least two of the following: fever, leukocytosis, graft tenderness and an increase in serum creatinine. All patients received bolus doses of methylprednisolone for 3 consecutive days during the rejection episode. All patients were studied on the 3rd day of bolus dosing and received 250 mg methylprednisolone by an i.v. infusion. In phase II, 4 patients were studied during a period of stable renal function when the methylprednisolone was given at lower chronic immunosuppressive doses. Serum samples were taken prior to infusion and serially over the following 24 hours. The serum samples were analyzed for methylprednisolone with high-performance liquid chromatography (HPLC) and pharmacokinetic parametes were generated. During rejection episodes, the methylprednisolone clearance values were 523 +/- 154 ml/h/kg with a corresponding mean volume of distribution of 1.89 +/- 0.72 l/kg. The mean methylprednisolone half-life was 2.61 +/- 0.62 h. During Phase II, the methylprednisolone clearance was 358 +/- 95 ml/h/kg with a half-life of 3.05 h. This observation indicates that methylprednisolone metabolism is increased during acute rejection compared to that seen during chronic immunosuppressive dosing with this agent.
Tornatore
K M
KM
Department of Pharmacy Practice, School of Pharmacy, State University of New York at Buffalo 14260, USA.
Walshe
J J
JJ
Reed
K
K
Venuto
R C
RC
D000208:Acute Disease; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D016030:Kidney Transplantation / Q000502:physiology; D008297:Male; D008657:Metabolic Clearance Rate; D008775:Methylprednisolone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014184:Transplantation, Homologous
D003404:Creatinine; D008775:Methylprednisolone