Gastrointestinal tract cytotoxic drugs

Further studies have validated this hypothesis, in part,4 and ultimately this inventive premise was borne out in clinical practice. As a result, 5-FU (5) was eventually approved for treatment of solid tumors, such as breast, colorectal, and gastric cancers. Marketed as Adrucil when administered intravenously, 5-FU can be used either as monotherapy or combination therapy with various cytotoxic drugs and biochemical modulators, such as leucovorin and methotrexate.5 Because 5-fluorouracil is not orally bioavailable, it must be administered by continuous infusion to optimize its efficacy due to its short half-life in plasma. In addition, 5-FU has poor selectivity toward tumors in vivo, and its distribution into tissues such as bone marrow, the gastrointestinal tract, the liver and skin causes high incidences of toxicity. In addition, in spite of its limited lipid solubility, 5-fluorouracil diffuses readily across the blood-brain barrier into cerebrospinal fluid and brain tissue.1,5... 

Rapidly proliferating cells, such as the bone marrow, gastrointestinal tract mucosa, hair follicles, and gonads are the most sensitive to cytotoxic drugs. 

Shanahan F (2010) Gut microbes from bugs to drugs. Am J Gastroenterol 105 275-279 Sivropoulou A, Papanikolaou E, Nikolaou C et al (1996) Antimicrobial and cytotoxic activities of Origanum essential oils. J Agric Food Chem 44 1202-1205 Smith AH, Mackie RI (2004) Effect of condensed tannins on bacterial diversity and metabolic activity in the rat gastrointestinal tract. Appl Environ Microbiol 70 1104-1115 Smith AH, Zoetendal EG, Mackie RI (2005) Bacterial mechanisms to overcome inhibitory effects of dietary tannins. Microb Ecol 50 197-205... 

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