Inflammatory response: an unrecognised source of variability in the pharmacokinetics and pharmacodynamics of cancer chemotherapy.
An important limitation in the use of chemotherapy in cancer treatment is that cytotoxic agents have small margins of safety compared with other drugs. The largely unpredictable pharmacokinetics of cytotoxic agents contribute significantly to differences in toxicity and efficacy between individuals. Over the past few decades, evidence has accumulated that the inflammatory response to conditions such as infection, degenerative disease, and cancer can greatly affect the disposition of drugs. A more recent finding is that the presence of an inflammatory response identifies patients with more aggressive disease and may also compromise the pharmacodynamics of anticancer drugs. In this review, we discuss the changes in the pharmacokinetics of drugs caused by the presence of inflammation. Also, we discuss the modulating role of inflammatory mediators on the pharmacokinetics and pharmacodynamics of cytotoxic agents. We argue that, overall, these factors identify inflammatory response as a potentially important factor in the interindividual variability of response and toxic effects to cancer chemotherapy.
Slaviero
Kellie A
KA
Department of Pharmacology, University of Sydney, NSW, Australia.
Clarke
Stephen J
SJ
Rivory
Laurent P
LP
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism
D000970:Antineoplastic Agents; D016207:Cytokines; D003577:Cytochrome P-450 Enzyme System