Methylprednisolone disposition in renal transplant recipients receiving triple-drug immunosuppression.
Renal transplant patients commonly receive triple-drug immunosuppression with standardized doses of cyclosporine, azathioprine, and methylprednisolone. Although cyclosporine may decrease the clearance of oral prednisone, data are lacking for methylprednisolone, a glucocorticoid commonly prescribed via a standardized protocol for intravenous therapy and during periods of acute rejection. The disposition of methylprednisolone (doses: 10-60 mg/day) was examined in nine renal transplant patients during the post-transplant period (0.8-14 months). Plasma samples were collected over 24 hr and analyzed for methylprednisolone via HPLC. Pharmacokinetic parameters were determined by noncompartmental analysis. The mean total clearance of methylprednisolone was 379 ml/hr/kg (range 105-672) and the volume of distribution was 1.4 +/- 0.5 L/kg. The mean plasma half-life was 2.7 +/- 1.1 hr. When normalized to a 1 mg dose of methylprednisolone, the mean peak concentration at 1 hr was 10.0 +/- 3.5 ng/ml with an 8 hr concentration ranging from 0.3 to 5.5 ng/ml. An appreciable variability in methylprednisolone metabolism thus exists in renal transplant recipients receiving triple-drug immunosuppression. This may partially explain the variable response to steroid therapy during acute rejection episodes and chronic immunosuppression as well as the unpredictable occurrence of chronic steroid toxicity.
Tornatore
K M
KM
Department of Pharmacy, State University of New York, Buffalo 14260.
Morse
G D
GD
Jusko
W J
WJ
Walshe
J J
JJ
D000293:Adolescent; D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage; D003524:Cyclosporins / Q000008:administration & dosage; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008775:Methylprednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged
D003524:Cyclosporins; D007166:Immunosuppressive Agents; D001379:Azathioprine; D008775:Methylprednisolone