OBJECTIVE: Cyclosporine has been used for patients with nephrotic syndrome. Because of substantial inter- and intra-patient variability and a narrow therapeutic window, drug monitoring of cyclosporine is mandatory. To confirm the therapeutic effects of a cyclosporine microemulsion (CSAME), the absorption profile of the agent after preprandial administration was determined in steroid-resistant patients with refractory nephrotic syndrome. METHODS: Fourteen patients were enrolled into the study (mean age, 31.2+/-12; 6 men, 8 women). The patients received 1.5 mg/kg of cyclosporine 30 minutes before breakfast for 6 months. Blood cyclosporine concentration was measured 5 times serially: before administration (C0) and at 1-hour intervals until 4 hours after administration of cyclosporine (C1-C4). In addition, area under the concentration-time curve from 0-4 hours (AUC0-4) was calculated. RESULTS: After 6 months, CSAME showed marked improvement in proteinuria levels (8.3+/-4.8 g/day vs 0.8+/-0.4 g/day, p<0.001). No changes in serum creatinine and urea nitrogen levels were observed. In 83% of the patients, the CSAME peak concentration appeared within 1 hour after administration (C1). A strong positive correlation was noted between AUC0-4 and C1 (R2=0.90312) and C2 (R2=0.78431). The mean steroid (prednisolone) dose was 40 mg/day when CSAME treatment was started, but a lowering of the dose to 17.5 mg/day (p<0.001) was achieved at 6 months after CSAME therapy. CONCLUSION: Preprandial administration of CSAME is effective in steroid-resistant patients with refractory nephrotic syndrome. C1 or C2, but not C0, was a good clinical marker for CSAME exposure.
OBJECTIVE:Cyclosporine has been used for patients with nephrotic syndrome. Because of substantial inter- and intra-patient variability and a narrow therapeutic window, drug monitoring of cyclosporine is mandatory. To confirm the therapeutic effects of a cyclosporine microemulsion (CSAME), the absorption profile of the agent after preprandial administration was determined in steroid-resistant patients with refractory nephrotic syndrome. METHODS: Fourteen patients were enrolled into the study (mean age, 31.2+/-12; 6 men, 8 women). The patients received 1.5 mg/kg of cyclosporine 30 minutes before breakfast for 6 months. Blood cyclosporine concentration was measured 5 times serially: before administration (C0) and at 1-hour intervals until 4 hours after administration of cyclosporine (C1-C4). In addition, area under the concentration-time curve from 0-4 hours (AUC0-4) was calculated. RESULTS: After 6 months, CSAME showed marked improvement in proteinuria levels (8.3+/-4.8 g/day vs 0.8+/-0.4 g/day, p<0.001). No changes in serum creatinine and ureanitrogen levels were observed. In 83% of the patients, the CSAME peak concentration appeared within 1 hour after administration (C1). A strong positive correlation was noted between AUC0-4 and C1 (R2=0.90312) and C2 (R2=0.78431). The mean steroid (prednisolone) dose was 40 mg/day when CSAME treatment was started, but a lowering of the dose to 17.5 mg/day (p<0.001) was achieved at 6 months after CSAME therapy. CONCLUSION: Preprandial administration of CSAME is effective in steroid-resistant patients with refractory nephrotic syndrome. C1 or C2, but not C0, was a good clinical marker for CSAME exposure.