Pharmacokinetics of Cyclosporin in Nephrotic Syndrome

This is a prospective study on ten children using Cyclosporin-A (CSA) microemulsion to treat idiopathic nephrotic syndrome (INS), with normal renal function, who achieved complete remission with CSA. The objective is to compare the pharmacokinetic (PK) parameters of CSA in INS during remission and relapse of the disease. The PK profile of CSA was evaluated with the 12-hour area under the time-concentration curve (AUC0-12) using seven time-point samples. This procedure was done on each patient during remission and relapse with the same CSA dose in mg/kg/day. The AUC0-12 was calculated by trapezoidal rule. All PK parameters and the resumed 4-hour area under the time-concentration curve (AUC0-4) were correlated with AUC0-12. This study is very important because the cyclosporin is a nephrotoxic drug with narrow therapeutic window.

Inclusion criteria

• children with steroid-resistant nephrotic syndrome and steroid-dependent nephrotic syndrome in use of cyclosporine
• renal function evaluated by creatinine clearance estimated by stature ≥ 90 ml/min/1.73m2
• cyclosporine trough level (C0) between 50 and 150 ng/ml
• complete remission with cyclosporine according to the guidelines of International Society of Kidney Diseases in Children

Exclusion criteria

• renal and hepatic function abnormalities
• presence of infectious disease
• clinical or histological signs of CSA nephrotoxicity and suspicious of non-compliance