The pharmacokinetics and pharmacodynamics of fludarabine in rheumatoid arthritis.

Abstract:

STUDY OBJECTIVE:To describe the pharmacokinetics and pharmacodynamics of fludarabine in patients with rheumatoid arthritis (RA). DESIGN:Open-label, staggered trial conducted in conjunction with a phase I-II clinical trial. SETTING:Government research hospital. PATIENTS:Twenty-six patients with refractory RA. INTERVENTION: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). MEASUREMENTS AND MAIN RESULTS: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. CONCLUSION: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.

journal_name

Pharmacotherapy

journal_title

Pharmacotherapy

authors

Knebel W,Davis JC Jr,Sanders WD,Fessler B,Yarboro C,Pucino F,Boumpas DT

subject

Has Abstract

pub_date

1998-11-01 00:00:00

pages

1224-9

issue

6

eissn

0277-0008

issn

1875-9114

journal_volume

18

pub_type

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