Fludarabine pharmacokinetics after subcutaneous and intravenous administration in patients with lupus nephritis

Study Objective. To compare the pharmaco kinetics of subcutaneous and intra venous fludarabine in patients with lupus nephritis. Design. Open-label, randomized, crossover trial conducted with a phase I-II trial. Setting. Government research hospital. Patients. Five patients with lupus nephritis. Intervention. Fludarabine 30 mg/m(2)/day was administered either subcutaneo usly or as a 0.5-hour intravenous infusion for 3 consecutive days. All pati ents received oral cyclophosphamide 0.5 g/m(2) on the first day of each cyc le. Measurements and Main Results. Plasma samples were collected before and 0.5 , 1, 1.5, 2, 4, 8, and 24 hours after the first dose. Urine was collected a t 6-hour intervals for 24 hours. Plasma and urine were analyzed for fluoroa rabinofuranosyladenine (F-ara-A), fludarabine's main metabolite, using high -performance liquid chromatography. Compartmental techniques were used to d etermine the pharmacokinetics of F-ara-A; a linear two-compartment model be st described them. Comparison of the pharmacokinetics between subcutaneous and intravenous administration was done by using, a Wilcoxon signed rank te st. No significant differences were found between subcutaneous and intraven ous administration in median (interquartile range) maximum concentrations o f 0.51 (038-0.56) and 0.75 (0.52-0.91) mg/L, respectively, or in fitted are a under the concentration-time curves from 0-24 hours of 4.65 (4.17-4.98) a nd 4.55 (3.5-4.94) mg(.)hour/L, respectively. Bioavailability of F-ara-A af ter subcutaneous dosing was approximately 105% of the bioavailability after intravenous administration. Differences in renal clearance and percentage of dose excreted in urine for subcutaneous and intravenous administration w ere nonsignificant. No injection site reactions were seen with subcutaneous dosing. Conclusion. Subcutaneous and intravenous administration of fludarabine appe ar to have similar pharmacokinetics in patients with lupus nephritis. Subcu taneous injection may offer a convenient alternative to intravenous adminis tration.