Pharmacokinetics of high-dose methotrexate in dogs: an experimental model with diffusion chambers

The usefulness of a diffusion chamber method for determination of concentrations of cytostatic drugs in the interstitial fluid of tissues was tested. Chambers with a permeable membrane (pore size: 0.45 micrometer) were implanted in the liver, kidney, bladder wall, and prostate of dogs. After administration of high doses of methotrexate (100 mg/kg body wt) the concentrations in the chamber fluid and in serum were measured simultaneously and repeatedly for 72 h. The method proved to be effective for collecting data on the distribution of drugs in different organs. The results show that knowledge of the serum concentration does not permit predictions of the drug concentration in the interstitial fluid of various tissues to be made.