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Related Experiment Videos

Constant intraperitoneal 5-fluorouracil infusion through a totally implanted system.

J W Gyves, W D Ensminger, P Stetson

    Clinical Pharmacology and Therapeutics
    |January 1, 1984
    PubMed
    Summary

    Continuous intraperitoneal 5-fluorouracil (FU) infusion in patients achieved high peritoneal concentrations and improved total body clearance (TBC) compared to bolus delivery. This method demonstrated acceptable toxicity, with chemical peritonitis as the dose-limiting factor.

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    Area of Science:

    • Pharmacology
    • Clinical Trials
    • Drug Delivery Systems

    Background:

    • 5-fluorouracil (FU) is a chemotherapeutic agent.
    • Intraperitoneal (IP) drug delivery aims to achieve higher local concentrations and reduce systemic toxicity.
    • Phase I clinical trials evaluate drug safety, dosage, and pharmacokinetics.

    Purpose of the Study:

    • To assess the pharmacokinetics and toxicity of continuous 5-day intraperitoneal infusions of 5-fluorouracil (FU) in a Phase I clinical pharmacology study.
    • To compare the total body clearance (TBC) and regional drug advantage of continuous IP FU infusion versus bolus IP FU administration.

    Main Methods:

    • Five patients received 20 courses of continuous 5-day IP FU infusions via an implanted catheter/port system.
    • Kinetic parameters and toxicity were evaluated for all courses.

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  • Pharmacokinetic data, including steady-state plasma and peritoneal concentrations, TBC, and permeability-area (PA) product, were analyzed.
  • Comparison of IP constant infusion versus bolus kinetics was performed in one patient.

    • Main Results:

    • A 2-3 log FU concentration differential was maintained between the peritoneal cavity and plasma.
    • Steady-state IP FU concentrations averaged 697 microM, while plasma concentrations averaged 0.34 microM.
    • Mean TBC was 18.4 L/min, with a mean PA product of 13.7 mL/min.
    • Continuous IP FU infusion resulted in a higher TBC (29.5 L/min) compared to bolus IP FU (14.3 L/min) in one patient.
    • Calculations indicated 75% drug extraction during peritoneal-to-systemic circulation, likely hepatic.

    Conclusions:

    • Continuous IP FU infusion offers an improved regional advantage over bolus IP FU due to increased TBC.
    • The toxicity profile was acceptable, with moderate chemical peritonitis being the dose-limiting toxicity in repeated courses.
    • No myelosuppression, alopecia, nausea, or vomiting were observed.