Skip to main content
main-content

11.10.2019 | Original Article

Pharmacokinetic and toxicodynamic evaluation of 5-fluorouracil administration after major hepatectomy in a rat model

Zeitschrift:
Cancer Chemotherapy and Pharmacology
Autoren:
Kazuhiro Tada, Yukio Iwashita, Ken Shiraiwa, Hiroki Uchida, Yusuke Oshima, Yuhki Sato, Hiroaki Nakanuma, Teijiro Hirashita, Takashi Masuda, Yuichi Endo, Yu Takeuchi, Masayuki Ohta, Hiroki Itoh, Masafumi Inomata
Wichtige Hinweise

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Abstract

Background

Chemotherapy after hepatectomy for colorectal liver metastasis has not been established, due to the toxic side effects, which are likely related to impaired drug clearance during liver regeneration. We investigated the pharmacokinetic and toxicodynamic evaluation of 5-fluorouracil (5-FU) during liver regeneration after major hepatectomy in a rat model.

Methods

Thirty-six male Wistar rats were divided into control (C), control with chemotherapy (CC), hepatectomy (H), and hepatectomy with chemotherapy (HC) groups. The CC and HC groups were administered 5-FU for 4 days. Plasma 5-FU, liver weight, and liver dihydropyrimidine dehydrogenase (DPD) were measured. The ileal villous height was measured to determine adverse effects.

Results

The area under the curve and maximum plasma concentration of 5-FU increased by up to 51% and 32%, respectively, in the HC group compared to the CC group. The liver regeneration rate was significantly lower in the HC group than in the H group (67.3 ± 7.4 vs 33.0 ± 5.7%, p < 0.001). The HC group had a significantly lower liver DPD than the CC group (4.4 ± 1.1 mg vs 6.9 ± 1.1 mg, p < 0.01). The HC group had a significantly lower ileal villous height than the CC group (253 ± 40 μm vs. 318 ± 36 μm, p < 0.05).

Conclusions

Reduction of the total liver DPD following major hepatectomy caused increased plasma 5-FU levels and 5-FU-associated toxicity.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

★ PREMIUM-INHALT
e.Med Interdisziplinär

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de. Zusätzlich können Sie eine Zeitschrift Ihrer Wahl in gedruckter Form beziehen – ohne Aufpreis.

Jetzt e.Med zum Sonderpreis bestellen!

Weitere Produktempfehlungen anzeigen
Literatur
Über diesen Artikel
  1. Sie können e.Med Innere Medizin 14 Tage kostenlos testen (keine Print-Zeitschrift enthalten). Der Test läuft automatisch und formlos aus. Es kann nur einmal getestet werden.

  2. Das kostenlose Testabonnement läuft nach 14 Tagen automatisch und formlos aus. Dieses Abonnement kann nur einmal getestet werden.


 

Neu im Fachgebiet Onkologie

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Onkologie und bleiben Sie gut informiert – ganz bequem per eMail.

Bildnachweise