Clinically, both
prednisolone and
prednisolone sodium succinate are widely used as
immunosuppressive agents for the treatment of various allergic disorders. However, whether
prednisolone sodium succinate itself has immunosuppressive or anti-inflammatory effects is unclear, and
prednisolone sodium succinate may exhibit its efficacy only after hydrolytic conversion to
prednisolone in-vivo. If this is the case, the impairment of
prednisolone sodium succinate conversion to
prednisolone in some clinical conditions may attenuate the efficacy of
prednisolone sodium succinate. We therefore compared the pharmacological efficacy of
prednisolone with that of
prednisolone sodium succinate in-vitro using human peripheral blood mononuclear cells (PBMCs). PBMCs were obtained from 5 healthy subjects and 1 patient with
pneumonia. The cells were incubated in the presence of
concanavalin A and the cell growth was estimated by 3-(4,5-dimethyl thiazo-2-yl)-2,5-diphenyl tetrazolium
bromide (MTT) assay. Both
prednisolone and
prednisolone sodium succinate dose-dependently suppressed PBMC blastogenesis. Mean (s.d.)
prednisolone and
prednisolone sodium succinate IC50 (concentration of
drug that gave 50% inhibition of cell growth) values were 580.0 (1037.9) and 3237.1 (4627.3) nM, respectively. The ratio of
prednisolone IC50/
prednisolone sodium succinate IC50 ranged from 0.005 to 0.230. Thus,
prednisolone sodium succinate potency was markedly lower than that of
prednisolone. After incubation of PBMCs with 100 microM
prednisolone sodium succinate, 22.7-42.9 microM
prednisolone was liberated into the culture medium, as determined by HPLC. The ratio of
prednisolone liberation from
prednisolone sodium succinate was not affected by the presence of
fetal bovine serum or PBMC, or both, in the culture medium. These results suggested that the PBMC-suppressive effects of
prednisolone sodium succinate might be due, at least partially, to
prednisolone liberated from
prednisolone sodium succinate into the culture medium.
Prednisolone sodium succinate can be converted to
prednisolone in the absence of serum or PBMCs, but the ratio of this conversion was very slow (t(1/2) > 4 days). Therefore, impairment of the enzymatic conversion of
prednisolone sodium succinate to
prednisolone in some pathological conditions such as
liver diseases may result in attenuation of the clinical efficacy of
prednisolone sodium succinate.