indicine-n-oxide and indicine

(-)- and (+)-trachelanthic and (-)- and (+)-viridifloric acids were synthesized and their isopropylidene derivatives were regiospecifically coupled, at C-9, with (-)-retronecine obtained by hydrolysis of monocrotaline, isolated from Crotalaria spectabilis. Hydrolysis, followed by oxidation, led to the N-oxides of indicine, intermedine, lycopsamine, and the new nonnatural product, respectively. Each of these analogues was screened in the P388 lymphocytic leukemia system at the same time as indicine N-oxide, and the results were compared. Other related analogues were prepared and similarly screened and the results compared with those from indicine N-oxide.

Topics: Animals; Antineoplastic Agents; Leukemia P388; Magnetic Resonance Spectroscopy; Mice; Pyrrolizidine Alkaloids

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.

Topics: Adolescent; Adult; Antineoplastic Agents, Phytogenic; Child; Child, Preschool; Female; Half-Life; Humans; Infusions, Parenteral; Kinetics; Male; Neoplasms; Pyrrolizidine Alkaloids