Summary
The following study of cyclosporine pharmacokinetics was performed to investigate the effects of withdrawal of low-dose maintenance prednisolone (0.3–0.6 mg/kg body weight) from the routine immunosuppressive regimen given to 10 liver transplant recipients with stable liver function tests.
After oral administration of cyclosporine (6.4–10.3 mg/kg) whole blood concentrations were measured by radioimmunoassay (RIA) with both a specific monoclonal antibody detecting parent drug and a non-specific antibody additionally detecting a cross-section of metabolites.
Withdrawal of prednisolone produced no significant change in the mean time and concentration of maximum blood cyclosporine (3.3 h and 1160 μg/l, respectively), the initial and terminal elimination half-life (3.5 h and 18.4 h, respectively) and the area under the blood concentration versus time curve (AUC) measured with either the specific or non-specific monoclonal antibody.
Measurements with these two antibodies indicated that the terminal elimination of cyclosporine metabolites was more rapid than for the parent drug (half-life: 14.5 vs 18.4, respectively).
Similar content being viewed by others
References
Maurer G (1985) Metabolism of cyclosporine. Transplant Proc 17 [Suppl 1]: 19–26
Kronbach T, Fischer V, Meyer DU (1988) Cyclosporine metabolism in human liver. Identification of a cytochrome P-450 IIIgene family as the major cyclosporine metabolising enzyme explains interactions of cyclosporine with other drugs. Clin Pharmacol Ther 43: 630–635
Frey BM, Frey FJ (1982) Simultaneous measurements of prednisone, prednisolone and 6 beta-hydroxy-prednisolone in urine by high-performance liquid chromatography coupled with a radioactive detector. J Chromatogr 229: 283–292
Ost L (1984) Effect of cyclosporine on prednisolone metabolism. Lancet I: 451
Klintmalm G, Sawe J (1984) High-dose methylprednisolone increases plasma cyclosporine levels in renal transplant recipients. Lancet I: 731
Burckhart GJ, Ptachcinski RJ, Venkataramanan R, Iwatsuki S, Esquivel C, Van Thiel DH, Starzl TE (1986) Cyclosporine trough concentration monitoring in liver transplant recipients. Transplant Proc 18 [Suppl 5]: 188–193
Quesniaux V, Tees R, Schreier MH, Maurer G, Van Regenmoertel MAV (1987) Potential of monoclonal antibodies to improve therapeutic monitoring of cyclosporine. Clin Chem 33: 32–37
Rosano TG, Pell MA, Freed ZM, Dyles MT, Lempert N (1988) Cyclosporine and metabolites in blood from renal allograft recipients with nephrotoxicity, rejection or good renal function; comparative high-performance liquid chromatography and monoclonal radioimmunoassay studies. Transplant Proc 20: 330–338
Venkataramanan R, Huang ML, Delamos B, Burckart GJH, Ptachcinski RJ, Van Thiel DH, Starzl TE (1989) Steroid metabolism in liver transplant patients. Transplant Proc 21: 2452
Tredger JM, Naoumov NV, Steward CM, O'Grady JG, Grevel J, Niven AA, Kelman AW, Whiting B, Williams R (1988) Influence of biliary T-tube clamping on cyclosporine pharmacokinetics in liver transplant recipients. Transplant Proc 20 [Suppl 2]: 512–515
First MR, Schroeder TJ, Weiskittel P, Myre SA, Alexander JW, Pesce AJ (1989) Concomitant administration of cyclosporin and ketoconazole in renal transplant recipients. Lancet II: 1198–1201
Langhoff E, Madsen S, Flachs H, Olgaard K, Ladefoged J, Hvidberg EF (1985) Inhibition of prednisolone metabolism by cyclosporine in kidney-transplanted patients. Transplantation 39: 107–109
Griffin JA, Gomes da, Costa CA, Salaman JR (1987) A controlled trial of steroids in cyclosporine treated renal transplant recipients. Transplantation 43: 505–508
Hricik DE, Moritz C, Mayes JT, Schulak JA (1990) Association of the absence of steroid therapy with increased cyclosporine blood levels in renal transplant recipients. Transplantation 49: 221–223
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Arnold, J.C., O'Grady, J.G., Tredger, J.M. et al. Effects of low-dose prednisolone on cyclosporine pharmacokinetics in liver transplant recipients: radioimmunoassay with specific and non-specific monoclonal antibodies. Eur J Clin Pharmacol 39, 257–260 (1990). https://doi.org/10.1007/BF00315106
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00315106