Monitoring of Blood Cyclosporine Concentration in Steroid-Resistant Nephrotic Syndrome

Abstract

Objective Cyclosporine has been used for patients with nephrotic syndrome. Because of substantial interand 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 (R 2 =0.90312) and C2 (R 2 =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.

Therapeutic drug monitoring of cyclosporine microemulsion in interstitial pneumonia with dermatomyositis

“…AUC 0-6 , which most markedly reflects the immunosuppressive effect, was significantly correlated with all sampling points after CSA administration, especially C2, but not C0. It has also been reported that AUC most strongly correlated with C2 while it was not correlated with C0 in the transplantation field [7] and that AUC was correlated with C2 in psoriasis and nephritic syndrome [9,10]. Our study is the first report to reveal the dynamics of the blood CSA level in the field of CVD, in which the importance of C2 monitoring was clarified.…”

Clinical practice guideline for pediatric idiopathic nephrotic syndrome 2013: medical therapy

“…Similar to the starting dosage used in kidney transplant patients, this guideline also recommends to maintain a trough level of 100-150 ng/mL for the first 3 months before remission, and for patients treated with cyclosporine for more than 1 year, to maintain a trough level of 60-80 ng/mL from the second year of the treatment. For children with steroid-resistant nephrotic syndrome, although dose adjustment according to C2 (blood concentration at 2 h post-dose) has not been established, some reports described a correlation between the AUC 0-4 (area under the concentration curve) of cyclosporine and C2 [43], or C2 control in children with frequently-relapsing nephrotic syndrome and in adults with steroid-resistant nephrotic syndrome (A randomized controlled trial of cyclosporine C2 monitoring; UMIN ID, C000000008) [126,127]. Evidence is expected to accumulate regarding C2 control in children with steroidresistant nephrotic syndrome.…”

“…Because of high relapse rates of 10-76 % after withdrawal of cyclosporine, and another calcineurin inhibitor, tacrolimus, in the treatment of steroid-resistant nephrotic syndrome [120,121,127,129], prolonged cyclosporine therapy is often required. However, with concerns about cyclosporine nephrotoxicity, long-term remission rates and renal outcome require further evaluation.…”

Age effect on whole blood cyclosporine concentrations following oral administration in children with nephrotic syndrome

“…The reason why [14]. Some recent studies also demonstrated that preprandial administration of CyA provided a more stable absorption profile [9,18,23]. With administration preprandially or just before meal, the drug reaches the digestive tract prior to food, and subsequent entry of food into the digestive tract promotes bile secretion; this may be connected with the good absorption of CyA [14].…”

“…Even though Neoral® was administered, some patients showed a delay in absorption [20]. Recently, however, some reports indicated that preprandial administration of CyA provided a stable absorption profile [9,14,18,23]. Trough levels (C0) have traditionally been used to monitor CyA whole blood concentration in clinical practice.…”