Object's details: Pharmacokinetic Drug Interaction Study of Sorafenib and Morphine in Rats

Provider:Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

Description

Title:
Pharmacokinetic Drug Interaction Study of Sorafenib and Morphine in Rats
Creator:
Karbownik, Agnieszka;
Szkutnik-Fiedler, Danuta;
Grabowski, Tomasz;
Wolc, Anna;
Stanisławiak-Rudowicz, Joanna;
Jaźwiec, Radosław;
Grześkowiak, Edmund;
Szałek, Edyta
Description:
A combination of the tyrosine kinase inhibitor—sorafenib—and the opioid analgesic— morphine—can be found in the treatment of cancer patients. Since both are substrates of Pglycoprotein (P-gp), and sorafenib is also an inhibitor of P-gp, their co-administration may affect their pharmacokinetics, and thus the safety and efficacy of cancer therapy. Therefore, the aim of this study was to evaluate the potential pharmacokinetic drug–drug interactions between sorafenib and morphine using an animal model. The rats were divided into three groups that Received: sorafenib and morphine (ISOR+MF), sorafenib (IISOR), and morphine (IIIMF). Morphine caused a significant increase in maximum plasma concentrations (Cmax) and the area under the plasma concentration–time curves (AUC0–t, and AUC0–¥) of sorafenib by 108.3 (p = 0.003), 55.9 (p = 0.0115), and 62.7% (p = 0.0115), respectively. Also, the Cmax and AUC0–t of its active metabolite—sorafenib N-oxide—was significantly increased in the presence of morphine (p = 0.0022 and p = 0.0268, respectively). Sorafenib, in turn, caused a significant increase in the Cmax of morphine (by 0.5-fold, p = 0.0018). Moreover, in the presence of sorafenib the Cmax, AUC0–t, and AUC0–¥ of the morphine metabolite M3G increased by 112.62 (p < 0.0001), 46.82 (p = 0.0124), and 46.78% (p = 0.0121), respectively. Observed changes in sorafenib and morphine may be of clinical significance. The increased exposure to both drugs may improve the response to therapy in cancer patients, but on the other hand, increase the risk of adverse effects.
Object availability:
free access
Date:
2021.12.16
Type:
Article;
PeerReviewed
Language:
English
Format:
application/pdf
Relation: http://eprints.ibb.waw.pl/2125 ;http://doi.org/10.3390/pharmaceutics13122172 ;doi:10.3390/pharmaceutics13122172
Subject:
RM Therapeutics. Pharmacology
Identifier: http://eprints.ibb.waw.pl/2125/1/pharmaceutics-13-02172.pdf ;
Karbownik, Agnieszka and Szkutnik-Fiedler, Danuta and Grabowski, Tomasz and Wolc, Anna and Stanisławiak-Rudowicz, Joanna and Jaźwiec, Radosław and Grześkowiak, Edmund and Szałek, Edyta (2021) Pharmacokinetic Drug Interaction Study of Sorafenib and Morphine in Rats. Pharmaceutics, 13 (12). p. 2172. ISSN 1999-4923
Data provider:
Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

Similar objects

Pharmacokinetic Drug Interaction Study of Sorafenib and Morphine in Rats

Date:2021.12.16

Type:other

Boron Cluster Modification with Antiviral, Anticancer, and Modulation of Purinergic Receptors' Activities Based on the Nucleoside Structure

Date:2018.05.20

Type:text

Molecular Mechanism for Cellular Response to β-Escin and Its Therapeutic Implications

Date:2016

Type:other

Genetic engineering and molecular characterization of yeast strain expressing hybrid human-yeast squalene synthase as a tool for anti-cholesterol drug assessment

Date:2016

Type:other

Mycophenolic Acid Metabolites Acyl-Glucuronide and Glucoside Affect the Occurrence of Infectious Complications and Bone Marrow Dysfunction in Liver Transplant Recipients.

Date:2015

Type:image

Effect of recombinant Lactococcus lactis producing myelin peptides on neuroimmunological changes in rats with experimental allergic encephalomyelitis

Date:2016.10.03

Type:other

Dimeric Benzodiazepines as Peptide Mimetics to Overcome p53-Dependent Drug Resistance of Tumors

Creator:Speina, Elzbieta | Wilczek, Marcin | Mieczkowski, Adam

Date:2023.02.03

Type:other

Recombinant Mouse GM-CSF is glycosylated in transgenic tobacco and maintains its biological activity

Date:2009.12.28

Type:other

Federacja Bibliotek Cyfrowych

Object's details: Pharmacokinetic Drug Interaction Study of Sorafenib and Morphine in Rats

Description

Similar objects