H G Holford’s scientific contributions

Kidney transplant patients receive chronic prednisone and azathioprine for immunosuppression. However, the effect of azathioprine on prednisolone pharmacokinetics has not been determined in this population. Total and unbound prednisolone concentrations were determined, using high performance liquid chromatography and equilibrium dialysis, in eight kidney transplant patients following their usual oral maintenance dose of prednisone alone and concomitantly with their usual dose of azathioprine. The results showed no significant differences between the two groups in estimates of prednisolone plasma protein binding parameters and peak time, peak concentration, mean input time, clearance/F, volume of distribution/F, or half-life (t 1/2), using total or unbound prednisolone concentrations. Thus, the concomitant administration of azathioprine does not appear to alter the bioavailability or elimination of prednisolone at these doses.