Clinical Drug-Drug Interaction Between Vatiquinone, a 15-Lipoxygenase Inhibitor, and Rosuvastatin, a Breast Cancer Resistance Protein Substrate.
Clin Pharmacol Drug Dev
; 12(3): 279-286, 2023 03.
Article
em En
| MEDLINE
| ID: mdl-36478438
ABSTRACT
Vatiquinone is a small-molecule inhibitor of 15-lipoxygenase in phase 3 development for patients with mitochondrial disease and Friedreich ataxia. The objective of this analysis was to determine the effect of vatiquinone on the pharmacokinetic profile of rosuvastatin, a breast cancer resistance protein substrate. In vitro investigations demonstrated potential inhibition of BCRP by vatiquinone (half maximal inhibitory concentration, 3.8 µM). An open-label, fixed-sequence drug-drug interaction study in healthy volunteers was conducted to determine the clinical relevance of this finding. Subjects received a single dose of 20-mg rosuvastatin followed by a 7-day washout. On days 8 through 14, subjects received 400 mg of vatiquinone 3 times daily. On day 12, subjects concomitantly received a single dose of 20-mg rosuvastatin. The geometric mean ratio for maximum plasma concentration was 77.8%; however, the rosuvastatin disposition phase appeared unaffected. The geometric mean ratios for the area under the plasma concentration-time curve from time 0 to time t and from time 0 to infinity were 103.2% and 99.9%, respectively. Mean rosuvastatin apparent elimination half-life was similar between treatment groups. These results demonstrate that vatiquinone has no clinically relevant effect on the pharmacokinetics of rosuvastatin.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Inibidores de Hidroximetilglutaril-CoA Redutases
Limite:
Female
/
Humans
Idioma:
En
Revista:
Clin Pharmacol Drug Dev
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos