Pharmacokinetics of the Akt Serine/Threonine Protein Kinase Inhibitor, Capivasertib, Administered to Healthy Volunteers in the Presence and Absence of the CYP3A4 Inhibitor Itraconazole.
clinical pharmacology
clinical research
drug-drug interactions
oncology
pharmacokinetics and drug metabolism
Journal
Clinical pharmacology in drug development
ISSN: 2160-7648
Titre abrégé: Clin Pharmacol Drug Dev
Pays: United States
ID NLM: 101572899
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
20
10
2022
accepted:
26
06
2023
medline:
4
9
2023
pubmed:
14
7
2023
entrez:
14
7
2023
Statut:
ppublish
Résumé
Capivasertib is a potent, selective inhibitor of all 3 Akt isoforms (Akt1/2/3), and it is currently being tested in Phase III trials for the treatment of prostate and breast cancer. To investigate the effect of a cytochrome P450 3A4 (CYP3A4) inhibitor on the pharmacokinetics of capivasertib, a Phase I drug-drug interaction study of capivasertib and itraconazole was conducted in 11 healthy volunteers (median age, 54 years). The 8-day study had 3 stages: Participants received a single dose of capivasertib 80 mg in Stage 1, 4 doses of itraconazole 200 mg over 3 days in Stage 2, and a final dose of capivasertib 80 mg coadministered with itraconazole 200 mg in Stage 3. Capivasertib pharmacokinetics were examined in Stages 1 and 3. Itraconazole coadministration increased the maximum plasma concentration of capivasertib and total capivasertib exposure (area under the concentration-time curve from time of administration to infinity) by 1.70-fold (90% confidence interval, 1.56-1.86) and 1.95-fold (90% confidence interval, 1.82-2.10), respectively.
Substances chimiques
capivasertib
WFR23M21IE
CYP3A4 protein, human
EC 1.14.14.55
Cytochrome P-450 CYP3A
EC 1.14.14.1
Cytochrome P-450 CYP3A Inhibitors
0
Itraconazole
304NUG5GF4
Protein Kinase Inhibitors
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Serine
452VLY9402
Threonine
2ZD004190S
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
856-862Informations de copyright
© 2023 AstraZeneca. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.
Références
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