Cancer chemotherapy and pharmacology
-
Cancer Chemother. Pharmacol. · May 2006
Randomized Controlled TrialClinical and pharmacokinetic study evaluating the effect of food on the disposition of 9-nitrocamptothecin and its 9-aminocamptothecin metabolite in patients with solid tumors.
9-Nitrocamptothecin (9NC) is an orally administered camptothecin analogue that has completed phase III trials for pancreatic cancer. In biological matrices, camptothecin analogues exist in equilibrium between the active-lactone (LAC) and inactive-hydroxy acid (HA) forms. 9NC has been administered on an empty stomach; however, it is unclear if food alters the absorption and disposition of 9NC and its 9-aminocamptothecin (9AC) active-metabolite. Thus, we evaluated the disposition of 9NC and 9AC after administration of 9NC under fasting conditions and after a standard meal. ⋯ Co-administration of 9NC with food reduces the oral absorption of 9NC; however, there was no difference in the exposure of 9AC. The is high interpatient variability in the effect of food on the absorption of 9NC and the interpatient variability in the effect of food on the disposition of 9AC is even greater when compared to 9NC.
-
Cancer Chemother. Pharmacol. · May 2006
Comparative StudyPreclinical pharmacology of the novel antitumor agent adaphostin, a tyrphostin analog that inhibits bcr/abl.
To define several pharmacological properties for the potential anticancer agent, adaphostin, in order to determine whether the compound is appropriate for clinical evaluation as an anticancer agent. ⋯ The stability of adaphostin in plasma varies with species. In mice and dogs dosed with adaphostin, plasma concentrations of the compound decreased rapidly. The clearance of adaphostin from plasma, on an m(2) basis, was equivalent for mice and rats but more rapid in dogs. These results are relevant for assessing the pharmacologic and toxicologic profiles and the antitumor activity of adaphostin in humans.