title: Antitumoral efficacy and pharmacokinetic properties of pirarubicin upon hepatic intra-arterial injection in the rabbit V x 2 tumour model.
abstract: To improve the efficiency of hepatic intra-arterial (h.i.a.) chemotherapy, we selected pirarubicin (THP) because it shows good properties for h.i.a. chemotherapy, such as fast and efficient cellular uptake, and used it for h.i.a. chemotherapy in rabbits with V x 2 tumour implanted in the liver. The anti-tumour effect of THP upon h.i.a. administration was compared with that upon intravenous (i.v.) injection and also with the anti-tumour activity of epirubicin (EPI) upon h.i.a. injection using optimal and maximal tolerated doses of each drug. When tumour growth rates and morphometric examinations were evaluated, it was found that THP and EPI were effective against V x 2 tumour when injected via the h.i.a. route. The activity of THP was stronger than that of EPI. As regards h.i.a. injection-related complication, plasma transaminase levels were temporarily elevated. To demonstrate higher anti-tumour activity and other advantages of h.i.a. injection of THP, plasma and tumour drug concentrations were determined by high-performance liquid chromatography after THP or EPI was administered at an equal dose to the rabbit V x 2 model. Hepatic intra-arterial injection of THP accomplished a selective and higher uptake into the tumour and lower effusion into the plasma than i.v. injection of THP or h.i.a. injection of EPL. Our findings indicate that THP is the better candidate of the two drugs tested for the h.i.a. chemotherapy because of its greater anti-tumour activity and the lower systemic drug exposure achieved upon h.i.a. injection.
authors.affiliation: Research Laboratories, Nippon Kayaku Co. Ltd., Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Okada
authors.forename: S
authors.initials: S
authors.lastname: Kudo
authors.forename: O
authors.initials: O
authors.lastname: Miyazaki
authors.forename: T
authors.initials: T
authors.lastname: Saino
authors.forename: H
authors.initials: H
authors.lastname: Ekimoto
authors.forename: H
authors.initials: H
authors.lastname: Iguchi
authors.forename: S
authors.initials: S
authors.lastname: Hirano
authors.forename: H
authors.initials: H
authors.lastname: Kuboki
authors.forename: H
authors.initials: H
authors.lastname: Kadosawa
authors.forename: T
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D001659:Biliary Tract / Q000187:drug effects; D001663:Bilirubin / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D015251:Epirubicin / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006499:Hepatic Artery; D007091:Image Processing, Computer-Assisted; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009368:Neoplasm Transplantation; D011817:Rabbits
chemical_list: D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; D004317:Doxorubicin; C027260:pirarubicin; D001219:Aspartate Aminotransferases; D001663:Bilirubin