Fate of tritiated didemnin B in mice: excretion and tissue concentrations after an intraperitoneal dose.

Abstract

Didemnin B has undergone trials in cancer patients, and has antiviral and immunosuppressive properties. [(3)H]didemnin B was administered intraperitoneally (i.p.) to mice at 320 or 1280 microg/kg. Urine and feces were collected until 168 h, at which time the mice were killed and tissues collected. Additionally, [(3)H]didemnin B was given i.p. at 320 microg/kg, and mice were killed at 1-120 h post-dosing. Radiolabel increased rapidly in blood then rapidly declined. Most radiolabel in urine, feces and tissues represented parent compound. Concentrations of [(3)H]didemnin B were greatest in the liver > gallbladder > lower digestive tract congruent with pancreas > spleen > kidney congruent with adipose tissue congruent with urinary bladder with urine. The pancreas had the longest terminal half-life of the tissues and the highest radioactivity at 7 days. Intermediate concentrations were in the duodenum congruent with jejunum > lung > iliopsoas > stomach congruent with testes congruent with skin > heart. Low concentrations were in the humerus congruent with femur congruent with quadriceps congruent with triceps >> brain. Fecal excretion accounted for 45.9%-58.3% of the dose and declined after 24 h, followed by an increase, suggesting possible enterohepatic recycling or an impact of circadian rhythms. Urinary excretion accounted for 18.4%-25.2% of the dose, but was minimal after 24 h. The concentrations were highest in organs previously found to be sensitive in animals and humans. Didemnin B should be evaluated in animal models for treatment of pancreatic cancer.

• Authors: Val R Beasley, Sally J Bruno, John S Burner, Byoung W Choi, Kenneth L Rinehart, Gary D Koritz, Jeffrey M Levengood
• Journal: Biopharmaceutics & drug disposition (Biopharm Drug Dispos) Vol. 26 Issue 8 Pg. 341-51 (Nov 2005) ISSN: 0142-2782 [Print] England
• PMID: 16082719 (Publication Type: Journal Article)
• Copyright: Copyright (c) 2005 John Wiley & Sons, Ltd.

Chemical References

• Antineoplastic Agents
• Antiviral Agents
• Depsipeptides
• Immunosuppressive Agents
• Tritium
• didemnins

Topics

• Animals
• Antineoplastic Agents (pharmacokinetics)
• Antiviral Agents (pharmacokinetics)
• Depsipeptides (pharmacokinetics)
• Immunosuppressive Agents (pharmacokinetics)
• Injections, Intraperitoneal
• Male
• Mice
• Tissue Distribution
• Tritium