Knebel W, Davis J C, Sanders W D, Fessler B, Yarboro C, Pucino F, Boumpas D T
Clinical Pharmacokinetics Research Laboratory and Clinical Section, Clinical Center, Pharmacy Department, National Institutes of Health, Bethesda, Maryland 20892-1196, USA.
Pharmacotherapy. 1998 Nov-Dec;18(6):1224-9.
To describe the pharmacokinetics and pharmacodynamics of fludarabine in patients with rheumatoid arthritis (RA).
Open-label, staggered trial conducted in conjunction with a phase I-II clinical trial.
Government research hospital.
Twenty-six patients with refractory RA.
Fludarabine 20 or 30 mg/m2/day was administered as a 0.5-hour infusion for 3 consecutive days (1 cycle) for 6 months (1 cycle/mo).
Serial plasma samples were collected for pharmacokinetic analysis on day 2 of the first cycle of therapy. Relationships between pharmacokinetic parameters and hematologic and efficacy parameters were examined. The disposition of fludarabine was characterized by a two-compartment model. There were no differences in pharmacokinetics between the low- and high-dose groups. The mean+/-SD total clearance, volume of distribution at steady state, and beta-half-life were 13.68+/-5.1 L/hour, 170.08+/-86.5 L, and 10.9+/-3.1 hours, respectively. The volume of the peripheral compartment was approximately twice as large as the volume of the central compartment, indicating a significant amount of tissue distribution. No significant pharmacodynamic relationships were observed between pharmacokinetic parameters and hematologic and efficacy parameters.
Fludarabine pharmacokinetics in patients with RA are characterized by an intermediate-length distribution phase (approximately 40 min), terminal half-life of 10.9 hours, and significant amount of tissue distribution.
