PMID- 32605304
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 12
IP  - 7
DP  - 2020 Jun 28
TI  - Pharmacokinetic Interaction between Sorafenib and Atorvastatin, and Sorafenib and 
      Metformin in Rats.
LID - 10.3390/pharmaceutics12070600 [doi]
LID - 600
AB  - The tyrosine kinase inhibitor sorafenib is the first-line treatment for patients 
      with hepatocellular carcinoma (HCC), in which hyperlipidemia and type 2 diabetes 
      mellitus (T2DM) may often coexist. Protein transporters like organic cation (OCT) 
      and multidrug and toxin extrusion (MATE) are involved in the response to 
      sorafenib, as well as in that to the anti-diabetic drug metformin or 
      atorvastatin, used in hyperlipidemia. Changes in the activity of these 
      transporters may lead to pharmacokinetic interactions, which are of clinical 
      significance. The study aimed to assess the sorafenib-metformin and 
      sorafenib-atorvastatin interactions in rats. The rats were divided into five 
      groups (eight animals in each) that received sorafenib and atorvastatin 
      (I(SOR+AT)), sorafenib and metformin (II(SOR+MET)), sorafenib (III(SOR)), 
      atorvastatin (IV(AT)), and metformin (V(MET)). Atorvastatin significantly 
      increased the maximum plasma concentration (C(max)) and the area under the plasma 
      concentration-time curve (AUC) of sorafenib by 134.4% (p < 0.0001) and 66.6% (p < 
      0.0001), respectively. Sorafenib, in turn, caused a significant increase in the 
      AUC of atorvastatin by 94.0% (p = 0.0038) and its metabolites 2-hydroxy 
      atorvastatin (p = 0.0239) and 4-hydroxy atorvastatin (p = 0.0002) by 55.3% and 
      209.4%, respectively. Metformin significantly decreased the AUC of sorafenib (p = 
      0.0065). The AUC ratio (II(SOR+MET) group/III(SOR) group) for sorafenib was equal 
      to 0.6. Sorafenib did not statistically significantly influence the exposure to 
      metformin. The pharmacokinetic interactions observed in this study may be of 
      clinical relevance in HCC patients with coexistent hyperlipidemia or T2DM.
FAU - Karbownik, Agnieszka
AU  - Karbownik A
AD  - Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical 
      Sciences, 61-861 Poznan, Poland.
FAU - Szkutnik-Fiedler, Danuta
AU  - Szkutnik-Fiedler D
AD  - Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical 
      Sciences, 61-861 Poznan, Poland.
FAU - Czyrski, Andrzej
AU  - Czyrski A
AUID- ORCID: 0000-0003-1581-8326
AD  - Department of Physical Pharmacy and Pharmacokinetics, Poznan University of 
      Medical Sciences, 60-781 Poznan, Poland.
FAU - Kostewicz, Natalia
AU  - Kostewicz N
AD  - Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical 
      Sciences, 61-861 Poznan, Poland.
FAU - Kaczmarska, Paulina
AU  - Kaczmarska P
AD  - Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical 
      Sciences, 61-861 Poznan, Poland.
FAU - Bekier, Malgorzata
AU  - Bekier M
AD  - Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical 
      Sciences, 61-861 Poznan, Poland.
FAU - Stanislawiak-Rudowicz, Joanna
AU  - Stanislawiak-Rudowicz J
AD  - Department of Gynecological Oncology, University Hospital of Lord's 
      Transfiguration, 60-569 Poznan, Poland.
FAU - Karazniewicz-Lada, Marta
AU  - Karazniewicz-Lada M
AD  - Department of Physical Pharmacy and Pharmacokinetics, Poznan University of 
      Medical Sciences, 60-781 Poznan, Poland.
FAU - Wolc, Anna
AU  - Wolc A
AUID- ORCID: 0000-0003-1190-5713
AD  - Department of Animal Science, Iowa State University, Ames, IA 50011, USA.
AD  - Hy-Line International, Research and Development, Dallas Center, IA 50063, USA.
FAU - Glowka, Franciszek
AU  - Glowka F
AUID- ORCID: 0000-0002-6611-5789
AD  - Department of Physical Pharmacy and Pharmacokinetics, Poznan University of 
      Medical Sciences, 60-781 Poznan, Poland.
FAU - Grzeskowiak, Edmund
AU  - Grzeskowiak E
AD  - Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical 
      Sciences, 61-861 Poznan, Poland.
FAU - Szalek, Edyta
AU  - Szalek E
AD  - Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical 
      Sciences, 61-861 Poznan, Poland.
LA  - eng
GR  - 502-01-33114230-3553 (to N.K.) and 502-01-33114230-3557 (to P.K.)/Uniwersytet 
      Medyczny im. Karola Marcinkowskiego w Poznaniu/
PT  - Journal Article
DEP - 20200628
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC7408095
OTO - NOTNLM
OT  - atorvastatin
OT  - drug-drug interaction
OT  - metformin
OT  - pharmacokinetics
OT  - sorafenib
OT  - sorafenib N-oxide
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript; or in the decision to publish the results.
EDAT- 2020/07/02 06:00
MHDA- 2020/07/02 06:01
PMCR- 2020/07/01
CRDT- 2020/07/02 06:00
PHST- 2020/06/10 00:00 [received]
PHST- 2020/06/25 00:00 [revised]
PHST- 2020/06/26 00:00 [accepted]
PHST- 2020/07/02 06:00 [entrez]
PHST- 2020/07/02 06:00 [pubmed]
PHST- 2020/07/02 06:01 [medline]
PHST- 2020/07/01 00:00 [pmc-release]
AID - pharmaceutics12070600 [pii]
AID - pharmaceutics-12-00600 [pii]
AID - 10.3390/pharmaceutics12070600 [doi]
PST - epublish
SO  - Pharmaceutics. 2020 Jun 28;12(7):600. doi: 10.3390/pharmaceutics12070600.