Enhancing effect of bromovinyldeoxyuridine on antitumor activity of 5-fluorouracil against adenocarcinoma 755 in mice. Increased therapeutic index and correlation with increased plasma 5-fluorouracil levels.

摘要: A marked inhibition of the growth solid tumor adenocarcinoma 755 was achieved by combination 5-fluorouracil (5-FU) with bromovinyldeoxyuridine (BVDU). The therapeutic index (LD50/ED50) for BVDU plus 5-FU 8.1 and 3.9 upon intraperitoneal (i.p.) or oral (p.o.) administration, respectively. i.p. given alone 2.3, whereas p.o. no could be established because insufficient activity compound. Thus, increased significantly when combined BVDU. Pharmacokinetic studies revealed that administration plasma levels rapidly declined, but that, in BVDU, clearance 5-FU, especially following slowed down considerably. Antitumor correlated AUC (area under concentration x time curve), within range from 0.02 to 0.4 microgram/ml.