Decreased cyclosporine exposure during the remission of nephrotic syndrome

In this paper, we report the pharmacokinetics changes observed in seven children with steroid-resistant nephrotic syndrome (SRNS). They received cyclosporine A (CsA) microemulsion 6 mg/kg/day and, one week later, they were admitted to perform a 12-h pharmacokinetic profile with eight time sample points. The pharmacokinetic profile was repeated at 24 weeks of treatment, when all patients achieved remission. Blood concentration against time curves were constructed for each patient at weeks 1 and 24 of CsA treatment. Peak concentrations (C _max) and the time needed to reach peak concentrations (t _max) were directly determined from these plots. The area under the curve (AUC) was estimated by the trapezoidal rule. There was a statistically significant difference of the AUC, trough levels, and t _max between weeks 1 and 24, with a decrease of AUC from 5,211 ng*h/ml in week 1 to 3,289 ng*h/ml in week 24, the trough levels decreased from 157 ng/ml to 96 ng/ml, and the t _max decreased from 1.85 h to 1.00 h. The higher CsA bioavailability during the nephrotic state has to be considered when managing patients, since the target AUC cannot be the same throughout the treatment.