Bidirectional pharmacokinetic drug interactions between olaparib and metformin.
Drug–drug interactions
Metformin
Olaparib
Pharmacokinetics
Journal
Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519
Informations de publication
Date de publication:
10 Oct 2023
10 Oct 2023
Historique:
received:
16
06
2023
accepted:
10
09
2023
medline:
10
10
2023
pubmed:
10
10
2023
entrez:
10
10
2023
Statut:
aheadofprint
Résumé
Olaparib is a PARP (poly-ADP-ribose polymerase) inhibitor used for maintenance therapy in BRCA-mutated cancers. Metformin is a first-choice drug used in the treatment of type 2 diabetes. Both drugs are commonly co-administered to oncologic patients with add-on type 2 diabetes mellitus. Olaparib is metabolized by the CYP3A4 enzyme, which may be inhibited by metformin through the Pregnane X Receptor. In vitro studies have shown that olaparib inhibits the following metformin transporters: OCT1, MATE1, and MATE2K. The aim of the study was to assess the influence of 'the perpetrator drug' on the pharmacokinetic (PK) parameters of 'the victim drug' after a single dose. To evaluate the effect, the AUC Male Wistar rats were assigned to three groups (eight animals in each group), which were orally administered: metformin and olaparib (I Metformin did not affect the olaparib PK parameters. The AUC A single dose of metformin did not affect the PK parameters of olaparib, nor did it inhibit the olaparib metabolism, but olaparib significantly changed the metformin pharmacokinetics, which may be of clinical importance.
Identifiants
pubmed: 37815561
doi: 10.1007/s00280-023-04591-y
pii: 10.1007/s00280-023-04591-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
ID : NSB0000015
Informations de copyright
© 2023. The Author(s).
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