Advantages of triple therapy with mizoribine, cyclosporine and prednisolone over other types of triple and/or double therapy including cyclosporine for renal transplantation.

Abstract

Mizoribine (Mz) is an analogue of azathioprine (Az) with less hepatotoxicity, being extensively used as immunosuppressant in place of the latter agent especially in Japan. However, careful comparative studies of mizoribine (Mz), cyclosporine (Cy), and prednisolone (Pr) versus azathioprine (Az), Cy and Pr or Cy and Pr in renal allotranspalnt patients have not been reported. Retrospectively we compared triple therapy with Mz, Cy, and Pr (group I, n = 50) to triple therapy with Az, Cy and Pr (group II, n = 13) and/or double therapy with Cy and Pr (group III, n = 11) in one-haplotype-identical living related renal transplantations performed between Oct. 1984 through March 1989. Initial and maintenance doses of Cy in groups I and II were largely two thirds of those in group III. Patient and graft survival rates at 3 years in each group are 100% and 92% (group I), 100% and 91% (group II), and 91% and 82% (group III). There were no statistical differences in patient and graft survival rates between these three groups. The incidences of miscellaneous complications were the same in the groups. Bone marrow suppression, however, was significantly less in group I than in group II (P less than 0.005). Cy related nephrotoxicity was apparently less in groups I and II than in group III. Estimated US $5,000 in a year can be saved by immunosuppressive treatment in a patient of group I as compared to a patient in group III. Therefore, we conclude that triple therapy with Mz, Cy and Pr is superior to those with Az, Cy and Pr, and/or double therapy with Cy and Pr.

Study protocol: high-dose mizoribine with prednisolone therapy in short-term relapsing steroid-sensitive nephrotic syndrome to prevent frequent relapse (JSKDC05 trial)

“…Historically, mizoribine has been used to suppress rejection reactions in kidney transplantation [ 20 , 21 ], lupus nephritis [ 22 , 23 ] and rheumatoid arthritis. Mizoribine has also been reported to be effective as a treatment for IgA nephropathy [ 24 , 25 ].…”

Glucocorticoid Receptor Modulators Informed by Crystallography Lead to a New Rationale for Receptor Selectivity, Function, and Implications for Structure-Based Design

“…The first GR LBD crystal structure was disclosed using dex (Chart ), and subsequently, the GR LBD binding conformations of more steroidal GR agonists and one steroid antagonist emerged. − The binding mode of a class of flexible trifluoromethyl carbinol GR agonists (TFCs), for example, GSK 866, (Chart ) ,, was more recently described that occupies a novel channel originally observed in the crystal structure of A ring fused steroids such as deacyl cortivazol (Chart ). ,− Novel GR ligands showing enhanced selectivity, differentiated function (TA vs TR), and oral in vivo activity have been disclosed, yet little structural information has emerged to influence ligand design. − We surmised that novel GR ligands could be identified with differentiated function based on a unique complex within the GR LBD. Herein, we characterize compound 10 with several close analogues that represent the first members of a novel class of potent, selective, and orally active GR ligands, − the crystal structure of compound 10 within the GR LBD, and the structural basis for TR activity and selectivity versus the remaining steroid NHRs.…”