In vivo kinetics of magnetically targeted low-dose doxorubicin.

The in vivo kinetics of low-dose doxorubicin (0.05 mg/kg), entrapped in a carrier and magnetically targeted, were characterized in a rat tail model. Tissue concentrations of doxorubicin at a preselected target site and in various organs were followed over time. As late as 60 min postinjection, 3.7 microgram/g of drug was found at the target site with no detectable drug levels found in any organ. In comparison, a 100-fold higher dose (5.0 mg/kg iv) of free doxorubicin yielded drug concentrations of 1.8 microgram/g at the target site and 15.0 microgram/kg in the pooled organs. Therefore, 1% of the free intravenous dose targeted magnetically yielded approximately twice the local doxorubicin concentration at a preselected target site with no detectable systemic distribution. Magnetic targeting of particulate drug carriers to localized disease sites is suggested as an efficient method of obtaining high local drug concentrations and may reduce many unwanted side effects from unrestricted systemic circulation.

Hemoperfusion for methotrexate removal.

Removal of methotrexate by Amberlite XAD-4 hemoperfusion was determined in a patient with metastatic breast carcinoma. During 4 hr of hemoperfusion the plasma concentration of methotrexate fell from 5.5 x 10(-7) M TO 3.1 x 10(-7) M. After hemoperfusion methotrexate concentration increased as a consequence of multicompartmental pharmacokinetics to 5.5 x 10(-7) M and then slowly declined. Plasma methotrexate clearance decreased from 79 ml/min 30 min into hemoperfusion to 28 ml/min at the conclusion. In vitro clearance of methotrexate by 17 artificial kidneys, Amberlite XAD-4, and uncoated charcoal was determined. Uncoated charcoal had the greatest clearance of methotrexate of all the devices tested. We conclude that: (1) Amberlite XAD-4 transiently reduces plasma methotrexate concentration; (2) in vitro, charcoal hemoperfusion is more effective than XAD-4 in removing methotrexate; (3) as a consequence of the multicompartmental pharmacokinetics of methotrexate a postperfusion rebound in plasma methotrexate concentration is to be expected.