Abstract
Didemnin B has undergone trials in cancer patients, and has antiviral and immunosuppressive properties. [3H]didemnin B was administered intraperitoneally (i.p.) to mice at 320 or 1280 μg/kg. Urine and feces were collected until 168 h, at which time the mice were killed and tissues collected. Additionally, [3H]didemnin B was given i.p. at 320 μg/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 [3H]didemnin B were greatest in the liver > gallbladder > lower digestive tract ≅ pancreas > spleen > kidney ≅ adipose tissue ≅ 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 ≅ jejunum > lung > iliopsoas > stomach ≅ testes ≅ skin > heart. Low concentrations were in the humerus ≅ femur ≅ quadriceps ≅ 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.
Original language | English (US) |
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Pages (from-to) | 341-351 |
Number of pages | 11 |
Journal | Biopharmaceutics and Drug Disposition |
Volume | 26 |
Issue number | 8 |
DOIs | |
State | Published - Nov 2005 |
Externally published | Yes |
Keywords
- Didemnin B
- Fate
- Pancreas
- Pharmacokinetics
ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science
- Pharmacology (medical)