Pharmacokinetics of doxorubicin in isolated lung of dogs and humans perfused in vivo.

The pharmacokinetics of doxorubicin was investigated in the lungs of dogs and three pulmonary cancer patients perfused in situ. In the dogs, doxorubicin uptake increased with time but was saturable at perfusate concentrations above 20 nmol/ml. After 50 min, tissue levels were consistently higher than blood perfusate levels. The kinetics of doxorubicin uptake were well described by a simple diffusion model. Changes in the estimated kinetic model parameters suggested that the saturation of doxorubicin accumulation at higher concentrations was due to a decrease in the relative rate of uptake rather than a change in the rate of efflux. In the three human patients studied, doxorubicin accumulation in the perfused lung was considerably slower compared to dog lung, and the level of drug measured in human lung tumor biopsies was consistently less than surrounding tissue. The present study has shown that lung perfusion is technically feasible and may represent a means of delivering cytotoxic drugs to unresectable pulmonary tumors in humans.