Pharmacokinetics of Cyclosporine A and Its Therapeutic Effect in Children with Renal Diseases / 소아과

ABSTRACT

PURPOSE: To know the body handling properties and anti-proteinuric effect of cyclosporine A(CsA) in children with renal diseases, 34 patients with nephrotic syndrome or glomerular diseases were included to treatment trials and evaluated. METHODS: Microemulsion formula CsA, 5 mg/kg/day was administered orally in two divided doses for 9.3+/-4.6 months. Pharmacokinetic studies of CsA were done twice at beginning and closing of 12 months' CsA therapy. RESULTS: The steady state CsA pharmacokinetic parameters of 34 patients were as follows; Tmax1.64+/-0.84 hr, Cmax788+/-354 ng/dL, C1258.7+/-33.2 ng/mL, Cavg246+/-96 ng/mL, AUC2,949+/-1,156 ng hr/mL, Vd4.03+/-0.45 L/kg, CL9.69+/-2.27 L/hr, T1/25.31+/-2.37 hr. C2 was the best to predict the CsA AUC(R=0.896, P<0.001). Body surface area based dosage(mg/m2/d) correlates best with AUC. Intra-individual CsA pharmacokinetic changes were not found after 12 months' therapy. Anti-proteinuric effect of CsA was considerable; 88.9% of primary nephrotic syndrome and 62.5% of secondary glomerular diseases was responsive to CsA thearpy. There was no serious complication and CsA treatment was well tolerated by the pediatric patients. CONCLUSION: CsA therapy for difficult renal diseases with proteinuria was effective and safe. For better AUC prediction of CsA, body surface area based dosage(mg/m2/d) and C2 monitoring are recommended in children with renal diseases.