Assessment of converting from intravenous to oral administration of cyclosporin A in pediatric allogeneic hematopoietic stem cell transplant recipients

We studied the administration method during a transition period from continuous intravenous (i.v.) infusion to oral administration of cyclosporin A (CsA). Thirty-two pediatric hematopoietic stem cell transplant (HSCT) recipients, between the ages of 8 months and 15.6 years (median 7.1 years) participated in this study. The pharmacokinetic properties of CsA was evaluated during the transition period from i.v. to oral CsA. The daily oral dose of CsA was three times higher than the i.v. dose. Oral dosing began immediately after the continuous infusion was discontinued. Whole-blood CsA concentrations were measured by a monoclonal fluorescence polarization immunoassay (FPIA). The mean ± s.d. value of bioavailability (F), maximum concentration (C_max), half-life (t_1/2) of CsA were 43.1 ± 14.4%, 1135.3 ± 340.6 ng/ml and 3.1 ± 1.2 h, respectively. Mean clearance (CL) ± s.d. was 480.9 ± 103.7, 414.9 ± 137.1 and 320 ± 51.8 ml/h/kg in patients <20, 20-40 and >40 kg of body weight, respectively. The CsA CL of younger children was significantly greater than for older children (P = 0.044). CsA trough levels were maintained within the therapeutic range throughout the transition period. Therefore, our findings suggest that the immediate administration of an oral formulation, after discontinuation of the continuous infusion, would be practical and effective for routine clinical use.