PMID- 11349741
OWN - NLM
STAT- MEDLINE
DCOM- 20011004
LR  - 20190915
IS  - 0277-0008 (Print)
IS  - 0277-0008 (Linking)
VI  - 21
IP  - 5
DP  - 2001 May
TI  - Fludarabine pharmacokinetics after subcutaneous and intravenous administration in 
      patients with lupus nephritis.
PG  - 528-33
AB  - 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.
FAU - Kuo, G M
AU  - Kuo GM
AD  - Department of Pharmacy, Warren Grant Magnuson Clinical Center, National 
      Institutes of Health, Bethesda, Maryland 20892, USA.
FAU - Boumpas, D T
AU  - Boumpas DT
FAU - Illei, G G
AU  - Illei GG
FAU - Yarboro, C
AU  - Yarboro C
FAU - Pucino, F
AU  - Pucino F
FAU - Burstein, A H
AU  - Burstein AH
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - Pharmacotherapy
JT  - Pharmacotherapy
JID - 8111305
RN  - 0 (Antineoplastic Agents)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - FA2DM6879K (Vidarabine)
RN  - P2K93U8740 (fludarabine)
SB  - IM
MH  - Adult
MH  - Antineoplastic Agents/administration & dosage/*pharmacokinetics
MH  - Confidence Intervals
MH  - Cross-Over Studies
MH  - Cyclophosphamide/administration & dosage
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Injections, Subcutaneous
MH  - Lupus Nephritis/drug therapy/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Statistics, Nonparametric
MH  - Vidarabine/administration & dosage/analogs & derivatives/*pharmacokinetics
EDAT- 2001/05/15 10:00
MHDA- 2001/10/05 10:01
CRDT- 2001/05/15 10:00
PHST- 2001/05/15 10:00 [pubmed]
PHST- 2001/10/05 10:01 [medline]
PHST- 2001/05/15 10:00 [entrez]
AID - 10.1592/phco.21.6.528.34549 [doi]
PST - ppublish
SO  - Pharmacotherapy. 2001 May;21(5):528-33. doi: 10.1592/phco.21.6.528.34549.