Suppression of endogenous cortisol for evaluating pharmacodynamics of prednisolone in early allograft rejection in renal transplantation.
Concentrations of endogenous cortisol were examined in 34 kidney-transplant recipients by improved "high-performance" liquid chromatography. Ten recipients were treated with prednisolone and azathioprine, the others with prednisolone and cyclosporine. Peripheral serum samples were collected just before transplantation, daily for two weeks after the transplant, weekly until discharge for about two months, and then monthly or occasionally. Mean (+/- SD) cortisol concentrations, initially 145 +/- 87 micrograms/L, decreased immediately to 5.93 +/- 5.11 micrograms/L after transplant, remained at almost these same values for two months, and then swiftly increased to 51 +/- 59 micrograms/L by 1000 days. Cortisol concentrations within the period characterized by a cumulative dose of prednisolone at 300-700 mg were correlated significantly with the presence or absence of acute allograft rejection; patients with cortisol greater than 4 micrograms/L had a higher risk of rejection. The majority of stable patients showed cortisol concentrations between 1 and 4 micrograms/L throughout the cumulative prednisolone period characterized above. Concentrations less than 1 microgram/L after high-dose administration of methylprednisolone were accompanied by severe lung infection. We conclude that suppressed concentrations of endogenous cortisol, as assessed by highly specific HPLC, might provide a basis for predicting the therapeutic efficacy and adverse effects of prednisolone.
Oka
K
K
Division of Clinical Pharmacology, Tokyo College of Pharmacy, Japan.
Hirano
T
T
Shimodaira
H
H
Homma
M
M
Sakurai
E
E
Tamaki
T
T
Kozaki
M
M
D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D003524:Cyclosporins / Q000627:therapeutic use; D006084:Graft Rejection; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D016030:Kidney Transplantation; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D003524:Cyclosporins; D011239:Prednisolone; D001379:Azathioprine; D006854:Hydrocortisone