Understanding Disease-Drug Interactions in Cancer Patients: Implications for Dosing Within the Therapeutic Window.

The human inflammatory response can result in the alteration of drug clearance through effects on metabolizing enzymes or transporters. In this article we briefly review the theory of how cancer can lead to indirect changes in drug metabolism, review acute phase proteins and cytokines as markers of changes in cytochrome P450 (CYP) activity in cancer patients, and provide clinical case examples of how the inflammation in advanced cancer patients can lead to altered CYP-mediated drug clearance.

Assessment of toxicity reduction in wastewater effluent flowing through a treatment wetland using Pimephales promelas, Ceriodaphnia dubia, and Vibrio fischeri.

Effluent toxicity is regularly assessed with Ceriodaphnia dubia short-term chronic and Vibrio fischeri toxicity tests. Condition factor and hemotocrit of fish have recently been used to assess fish health following exposure to xenoestrogens in complex municipal effluents. To assess the ability of a treatment wetland to reduce or remove toxicity of a municipal effluent, we compared C. dubia and V. fischeri bioassays to Pimephales promelas responses in situ. Final whole effluent was diverted to a constructed wetland and effluent samples were taken daily from four sites, at incremental distances from the inflow, for a 3-week study. Overlapping 7-day C. dubia tests and V. fischeri assays were conducted with samples from each wetland site concurrent with a 3-week fish exposure. C. dubia survival and fecundity were significantly (< 0.0001) reduced at the inflow, but steadily improved with distance from the inflow. Fish condition and hematocrit were lower (alpha < 0.05) at wetland sites closer to the inflow than other wetland sites and laboratory controls. However, effluent toxicity was not detected by V. fischeri bioassays. Our findings indicate that 7-day C. dubia bioassays were most sensitive to effluent toxicity and suggest that other bioassays should be used concurrent with V. fischeri assays for municipal effluent toxicity testing.