Comparison of suppressive potency between prednisolone and prednisolone sodium succinate against mitogen-induced blastogenesis of human peripheral blood mononuclear cells in-vitro.
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.
Sugiyama
K
K
Division of Pharmacy, Niigata University Medical Hospital, Japan. sugiyama-nii@umin.ac.jp
Kawada
T
T
Sato
H
H
Hirano
T
T
D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology; D008934:Mitogens; D011014:Pneumonia; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*
D003470:Culture Media; D007166:Immunosuppressive Agents; D008934:Mitogens; D011239:Prednisolone; C021322:prednisolone hemisuccinate