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Dichloroallyl lawsone.

E M McKelvey, M Lomedico, K Lu

    Clinical Pharmacology and Therapeutics
    |May 1, 1979
    PubMed
    Summary
    This summary is machine-generated.

    Dichloroallyl lawsone (DCL) shows potential for cancer treatment but can cause heart toxicity. Pharmacokinetic studies in patients suggest limiting DCL doses to 450 mg/m2 to maintain safe plasma concentrations.

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    Area of Science:

    • Pharmacology
    • Oncology
    • Toxicology

    Background:

    • Dichloroallyl lawsone (DCL) is a synthetic analogue of lapachol with potential anticancer applications.
    • DCL exhibits low myelosuppression in animals but demonstrates acute cardiac toxicity in rhesus monkeys, correlated with peak plasma concentrations.

    Purpose of the Study:

    • To investigate the pharmacokinetics of DCL in human patients.
    • To establish safe dosage limits for DCL in Phase I clinical trials.

    Main Methods:

    • Administered radioactive [1- or 4-14C]DCL (10 mg/m2, 250 muCi/patient) via rapid intravenous infusion to four patients.
    • Monitored plasma concentrations of unchanged DCL, calculated half-lives, area under the curve (C X t), and clearance rate.

    Main Results:

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    • Mean peak plasma DCL concentration was 2.9 +/- 0.3 mg/L.
    • Mean initial plasma half-life was 48.9 +/- 19 min, with a terminal half-life of 20.3 +/- 1.8 hr.
    • Mean C X t was 50.1 +/- 12 mg/L/hr, and clearance rate was 0.08 ml/kg/min.

    Conclusions:

    • Pharmacokinetic data suggest a maximum dose of 450 mg/m2 for DCL administered via rapid intravenous infusion.
    • This dose limit aims to keep maximal plasma DCL concentrations below the observed toxic threshold of 130 mg/L in monkeys.