Cisplatin Pharmacokinetics in Nontumoral Pig Liver Treated With Intravenous or Transarterial Hepatic Chemoembolization

Chabrot, P.; Cardot, Jean‐Michel; Guibert, Pierre; Bouculat, François; Lucie, Cassagnes; Léger-Enreille, Anne; Buc, Emmanuel; Déchelotte, Pierre; Bommelaer, Gilles; Boyer, Louis; Abergel, Armand

doi:10.1007/s00270-012-0386-0

Cited by 1 publication

(1 citation statement)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Comparison of cisplatin pharmacokinetics in plasma and liver of minipigs after intravenous, intrahepatic arterial administration, and intrahepatic arterial administration with partial embolization using absorbable gelatin or complete embolization showed lower systemic exposure to cisplatin and decreased plasmatic terminal half-life after embolization, whereas hepatic exposure and terminal half-life were increased compared to intravenous administration. These results are in agreement with similar observations in patients after chemoembolization with other materials (Chabrot et al 2012). In this respect, the minipig models are supportive to explore and compare new chemoembolizaton procedures in order to increase local exposure of anticancer drugs in target tissues and reduce systemic toxicity.…”

Section: Minipig In Local Administration Of Anticancer Drugs: Chemoembolizationsupporting

confidence: 93%

The Potential of Minipigs in the Development of Anticancer Therapeutics

2015

View full text Add to dashboard Cite

Minipigs are increasingly being used as an alternative to dog or monkey in nonclinical safety testing of pharmaceuticals since they share similar anatomical and physiological characteristics to humans. Integrative assessment of pharmacodynamic and pharmacokinetic data sets of drug candidates from in silico, in vitro, and in vivo investigations form the basis for selecting the most relevant nonrodent species for toxicology studies. Developing anticancer therapeutics represents a special challenge for species selection due to their effects on multiple organ systems. The toxicological profile of anticancer drugs can be associated with steep dose-response curves, especially due to dose-limiting toxicity on the alimentary, hematopoietic, and immune systems. Selection of an appropriate species for toxicology studies is of importance to avoid an inappropriately low (without benefit for the late-stage cancer patient) or high clinical starting dose (with a risk of unexpected adverse reactions). Although the minipig has been the preferred species to develop drugs applied topically, it is only rarely used in anticancer drug development compared to dog and monkey. In this context, we discuss the potential of minipigs in anticancer drug development with examples of programs for oral and dermal administration, intravascular application in drug-eluting stents, and local chemotherapy (chemoembolization).

show abstract

Section: Minipig In Local Administration Of Anticancer Drugs: Chemoembolizationsupporting

confidence: 93%