Prednisone and prednisolone interconversion in the rabbit utilizing unbound concentrations

Prednisolone (POH) and prednisone (PO) were both administered via seven different intravenous infusions (three POH and four PO) in each of six rabbits to obtain steady state. Bolus doses of POH and PO were also administered to four of the rabbits. Plasma samples of POH and PO were analyzed by normal phase HPLC. Unbound concentrations of both compounds were estimated in each rabbit using equilibrium dialysis and computer fit of the nonlinear or linear binding. The unbound fraction of POH ranged between 3 and 15 per cent from tracer to total concentrations of 2000 micrograms-1. The unbound fraction of PO ranged between 23 and 34 per cent and appeared nonlinear for four of the rabbits. The mean apparent unbound clearances of POH ranged from 4.4 to 6.1 lh-1kg-1 and from 4.1 to 5.9 lh-1kg-1 for PO, and were dose-independent for both compounds. The available fraction of POH from PO was 50 to 70 per cent and independent of dose. The available fraction of PO from POH averaged 44 per cent at the low infusion rate decreasing to 16 and 20 per cent at the medium and high infusion rates. Although saturability in the formation of PO from POH was noted, this nonlinear step is apparently not large enough to induce observable changes from linearity in the overall disposition of unbound POH.