Fludarabine pharmacokinetics after subcutaneous and intravenous administration in patients with lupus nephritis.
OBJECTIVE
To compare the pharmacokinetics of subcutaneous and intravenous fludarabine in patients with lupus nephritis.


METHODS
Open-label, randomized, crossover trial conducted with a phase I-II trial.


METHODS
Government research hospital.


METHODS
Five patients with lupus nephritis.


METHODS
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.


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.


CONCLUSIONS
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.
Kuo
G M
GM
Department of Pharmacy, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
Boumpas
D T
DT
Illei
G G
GG
Yarboro
C
C
Pucino
F
F
Burstein
A H
AH
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016001:Confidence Intervals; D018592:Cross-Over Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008181:Lupus Nephritis / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine