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

Author(s): Kuo GM, Boumpas DT, Illei GG, Yarboro C, Pucino F, Burstein AH

Affiliation(s): Department of Pharmacy, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.

Publication date & source: 2001-05, Pharmacotherapy., 21(5):528-33.

Publication type: Clinical Trial; Clinical Trial, Phase I; Clinical Trial, Phase II; Randomized Controlled Trial

STUDY OBJECTIVE: To compare the pharmacokinetics of subcutaneous and intravenous 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/m2/day was administered either subcutaneously or as a 0.5-hour intravenous infusion for 3 consecutive days. All patients received oral cyclophosphamide 0.5 g/m2 on the first day of each cycle. 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 at 6-hour intervals for 24 hours. Plasma and urine were analyzed for fluoro-arabinofuranosyladenine (F-ara-A), fludarabine's main metabolite, using high-performance liquid chromatography. Compartmental techniques were used to determine the pharmacokinetics of F-ara-A; a linear two-compartment model best described them. Comparison of the pharmacokinetics between subcutaneous and intravenous administration was done by using a Wilcoxon signed rank test. No significant differences were found between subcutaneous and intravenous administration in median (interquartile range) maximum concentrations of 0.51 (0.38-0.56) and 0.75 (0.52-0.91) mg/L, respectively, or in fitted area under the concentration-time curves from 0-24 hours of 4.65 (4.17-4.98) and 4.55 (3.5-4.94) mg x hour/L, respectively. Bioavailability of F-ara-A after 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 were nonsignificant. No injection site reactions were seen with subcutaneous dosing. CONCLUSION: Subcutaneous and intravenous administration of fludarabine appear to have similar pharmacokinetics in patients with lupus nephritis. Subcutaneous injection may offer a convenient alternative to intravenous administration.

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