Practical aspects in the use of cyclosporin in paediatric nephrology

Abstract

Many factors must be considered for the effective and safe use of cyclosporin A (CsA) in paediatric nephrology. Detailed knowledge of the variable bioavailability, tissue distribution, and metabolism, as well as causes which lead to their alteration are necessary. Factors which affect the activity of the mixed function oxidase system cytochrome P-450 must be considered, i.e. liver dysfunction and many drugs. Precise knowledge of the CsA determination method and the spectrum of metabolites is essential. In children with renal transplants, a body surface area-related dose will better meet the dose requirements than a body weight related-dose. For drug level monitoring whole blood rather than plasma should be used, and the parent drug level should be the main determinant; elevated metabolite levels may be important in suspected nephrotoxicity or liver dysfunction. Pharmacokinetic profiles are necessary to discover absorption problems or increased CsA clearance rates which necessitate shorter dosing intervals. In children with steroid-dependent minimal change nephrotic syndrome, remission without steroids is maintained as long as CsA is given. The appropriate starting dosage is 150 mg/m2 per day; trough level monitoring is mandatory to prevent nephrotoxicity and to confirm adequate immunosuppressive drug levels which should be 80-160 ng/ml (parent drug level). Although the benefit of CsA has been reported in some cases of lupus erythematosus, its use should be restricted to severe cases only until its efficacy and safety has been confirmed in controlled trials.