Anthracyclines

Alteration of the Pharmacokinetics of COL-3, a Matrix Metalloproteinase Inhibitor, Due to Acute Gastrointestinal Toxicity of Doxorubicin

“…Lack of drug interaction between COL-3 and DOX in BDC rats suggested that the biliary excretion of DOX and its metabolites into the intestinal lumen was the source of drug interaction. It was likely that the presence of DOX in the GI tract was responsible for, in a large part, DOX's acute GI toxicity (i.e., mucositis), which has been widely reported in patients (33), and in the present study, severe diarrhea was noted in DOX-treated rats, especially those with bile-duct intact.…”

“…The acute diarrhea induced by DOX may stimulate intestinal contractility and disturb normal intestinal mucosa absorptive and secretory functions (33). The direct effect of DOX on the permeability of COL-3 across intestinal mucosa was demonstrated by the influence of DOX on the permeability of COL-3 across Caco-2 monolayers.…”

“…Similar to irinotecan hydrochloride (CPT-11), another cytotoxic agent, the cytotoxic activity of DOX and its active metabolite (i.e., doxorubicinol) can considerably damage GI mucosa cells both structurally and functionally (33). The acute diarrhea induced by DOX may stimulate intestinal contractility and disturb normal intestinal mucosa absorptive and secretory functions (33).…”