Immunosuppressive metabolites of cyclosporine in the blood of renal allograft recipients.

摘要: Cyclosporine levels by radioimmunoassay (RIA) and high-performance liquid chromatography (HPLC) were monitored in serial blood samples (n = 177) from 11 renal allograft recipients. HPLC analysis revealed three primary metabolites of CsA (M17, M1, M21) peak trough samples; M17 was the preponderant metabolite. In 4 patients on whom metabolite assays performed, found at 86-2004 ng/ml; M1 M21 up to 100 ng/ml. The immunosuppressive properties purified M17, M21, M8 (which not detected blood) compared with CsA. M17--and, a lesser extent, M21--were inhibit vitro response human mononuclear cells mixed leukocyte culture mitogen (phytohemagglutinin [PHA], concanavalin A [Con A], pokeweed [PWM]) 1000 exhibited no inhibitory activity. further tested 10-1000 ng/ml PHA lymphocyte (MLC) assays. had considerably less activity (12-43%) than (18-70%) assay. However, MLC experiments blocked proliferative 39-72% 100-800 ng/ml, which approached degree inhibition (63-87%). 34 37 (92%) patient samples, level exceed parent drug could be measured accurately RIA. observed (particularly M17) their presence recipients suggest possible role for these immunopharmacology