Disease relevance of Oxeclosporin

• Efficacy and tolerability of multiple-dose SDZ IMM 125 in patients with severe psoriasis [1].

High impact information on Oxeclosporin

• A comparative study of cyclosporine and its derivative SDZ IMM-125 in canine renal allografts [2].
• Our findings suggest that in rat hepatocyte cultures, SDZ IMM 125 is a specific inducer of apoptosis after short-term incubation, and this overlaps with necrosis after longer treatment periods [3].
• The specific caspase-3 inhibitor, Ac-Asp-Glu-Val-Asp-aldehyde, inhibited caspase-3 activation and attenuated SDZ IMM 125-induced apoptosis and lactate dehydrogenase leakage [3].
• SDZ IMM 125 induced weaker effects than CsA in terms of PASMC proliferation and ET-1 secretion [4].
• Furthermore, SDZ IMM 125 increased Na+ and Ca++ permeability across the liposomal membranes significantly more than CyA [5].

Biological context of Oxeclosporin

• After 20 h of SDZ IMM 125 incubation, the parameters of apoptosis were further increased [3].
• Sites of biotransformation for the cyclosporin derivative SDZ IMM 125 using human liver and kidney slices and intestine. Comparison with rat liver slices and cyclosporin A metabolism [6].
• SDZ IMM 125 distributes extensively in most tissues except in brain; multiple oral administration does not modify the tissue distribution and indicates that there is no drug accumulation [7].
• The results showed that SDZ-IMM-125 is immunosuppressive in dogs and prolongs graft survival up to 50 days at a dosage of 20 mg/kg/day [8].
• A comparison of CSA to its hydroxyethyl derivative SDZ IMM 125 (IMM) as to bioavailability to epidermal and dermal cells and the potential for inactivation by biotransformation was investigated using a human dermal skin model (skin2 ZK1100) and a barrier function model (skin2 ZK 1300) [9].

Anatomical context of Oxeclosporin

• The uptake of CyA and SDZ IMM 125 into freshly isolated rat hepatocytes was neither saturable, Na+ dependent or temperature sensitive, nor could it be inhibited vice versa, indicating passive diffusion [5].
• The aim of this study was to compare two types of cyclosporin (Cs) particles, SDZ OXL 400 and SDZ IMM 125, the latter being more hydrophilic, to understand their uptake by airway macrophages [10].
• We also tested the effect of SDZ IMM 125 in orthotopic small bowel transplantation with three combinations, namely host-versus-graft (HVG), graft-versus-host (GVH), and combined HVG and GVH immune responses and pancreas transplantation in the rat with different doses [11].
• Isolation, identification and immunosuppressive activity of SDZ-IMM-125 metabolites from human liver microsomes [12].
• Cyclosporine and its analogue SDZ IMM 125 mediate very similar effects on T-cell activation--a comparative analysis in vitro [13].

Associations of Oxeclosporin with other chemical compounds

• High dose (20 mg/kg/day) treatment of both SDZ IMM 125 and CsA led to abnormal recipient liver enzymes alanine aminotransferase and aspartate aminotransferase postoperatively [11].

Gene context of Oxeclosporin

• In humans, cytochrome P4503A (CYP3A) is the major cytochrome P450 gene family that metabolizes SDZ IMM 125 (IMM) to its primary metabolites [14].

Analytical, diagnostic and therapeutic context of Oxeclosporin

• At an equal dose of 15 mg/kg/day and in the same drug vehicle, SDZ IMM-125 was not superior to CsA in prolonging allograft survival [2].
• As observed by transmission electron microscopy, treatment with SDZ IMM 125 resulted in an increase in the number of necrotic cells after 20 h, but not after 4 h [3].
• After transplantation, SDZ-IMM-125 was given orally at a dosage of 5, 7.5, 10 or 20 mg/kg/day, and graft survival compared to that in dogs given cyclosporin 10 mg/kg or in untreated animals [8].
• The efficacy of SDZ IMM 125 in preventing allograft rejection was evaluated in kidney transplantation in the dog and orthotopic small bowel and heterotopic pancreas transplantation in the rat [11].

References