Disposition of total and unbound prednisolone in renal transplant patients receiving anticonvulsants

Gambertoglio, John G.; Holford, Nicholas H. G.; Kapusnik, Joan E.; Nishikawa, Reid; Saltiel, Manuel; Stanik-Lizak, Patricia; Birnbaum, Jytte L.; Hau, Toni; Amend Jr., William J. C.
January 1984
Kidney International;Jan1984, Vol. 25 Issue 1, p119
Academic Journal
Kidney transplant patients receiving phenytoin or phenobarbital may have decreased graft survival. These drugs have been shown to enhance the metabolism of glucocorticoids. We determined the disposition of total and unbound prednisolone in six stable kidney transplant patients receiving prednisone for immunosuppression and phenytoin or phenobarbital for a seizure disorder. Six similar patients not on anticonvulsants served as controls. A single intravenous dose of prednisolone was administered, and plasma samples were analyzed for prednisolone using a high-performance liquid chromatographic assay. Equilibrium dialysis was used to determine unbound prednisolone concentrations. Pharmacokinetic analysis showed that the half-life of prednisolone was shorter in the anticonvulsant group compared to the controls, based on both total (2.3 ± 0.4 vs. 3.4 ± 0.2 hr (SD), P < 0.01) and unbound (1.7 ± 0.3 vs. 2.4 ± 0.2 hr. P < 0.01) concentrations. Total drug clearance was 10.4 ± 2.8 liters/hr (0.171 ± 0.087 liters/hr, kg)in the anticonvulsant group versus 7.2 ± 1.2 liters/hr (0.1.00 ± 0.014 liters/hr · kg) in the controls (P < 0.05). Unbound prednisolone clearance was 57.2 ± 12.1 versus 46.4 ± 8.7 liters/hr (P > 0.05) and for weight-corrected estimates 0.886 ± 0.224 liters/hr, kg versus 0.644 ± 0.115 liters/hr, kg (P < 0.05) in the two groups, respectively. Thus, the disposition of prednisolone is altered by anticonvulsants in kidney transplant patients and may require dose alteration.


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