Pharmacokinetic study of indicine N-oxide in pediatric cancer patients

Abstract

Pharmacokinetics of the experimental antitumor agent indicine N-oxide were investigated in a group of 23 pediatric cancer patients. Plasma elimination of indicine N-oxide was best described by a two-compartment open model. The mean plasma distribution phase half-life, plasma elimination phase half-life, and plasma clearance were 8 min, 84 min, and 62 ml/min/m2 (2.1 ml/min/kg), respectively. One patient with renal impairment had an abnormally long plasma elimination phase half-life (275 min) and reduced plasma clearance (17 ml/min/m2). Plasma elimination phase half-life values increased and plasma clearance values decreased with increasing age of the pediatric patients. Plasma elimination of indicine N-oxide was more rapid in this group of children than in adults who had previously received the drug.

Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

“…Data are available for several purified DHPAs including riddelliine, senecionine, monocrotaline, and indicine N -oxide [20,21,22,23]. However, only a few of these studies were done using oral exposures which limits extrapolation to clinical disease due to the lack of absorption information.…”