PROBENECID INHIBITION OF METHOTREXATE CEREBROSPINAL FLUID PHARMACOKINETICS IN DOGS

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  • 1 January 1978
    • journal article
    • research article
    • Vol. 62  (10) , 1465-1470
Abstract
CSF and plasma concentrations of methotrexate (MTX) were followed in dogs for 72 h after intracisternal injection of MTX with and without probenecid pretreatment. CSF levels declined as a biexponential function of time. Probenecid pretreatment of the animals prolonged the second phase half-disappearance time of MTX from 5.20 .+-. 0.89 to 7.086 .+-. 0.23 h (mean .+-. SD). The peak mean plasma concentration of MTX was lower in the presence of probenecid. The rate of decline of plasma MTX concentrations was slower after treatment with probenecid, with mean half-disappearance times of 7.60 .+-. 0.77 and 11.32 .+-. 1.08 h. These CSF and plasma data support the proposal that probenecid inhibited the transfer of MTX from CSF to blood.