Impact of P-gp inhibition on systemic exposure of pralsetinib and dosing considerations.
Clin Transl Sci
; 17(6): e13818, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38807449
ABSTRACT
A study to determine the impact of cyclosporine (Neoral), an inhibitor of P-gp, on the pharmacokinetics of pralsetinib (trade name GAVRETO®) was conducted in 15 healthy adult volunteers. A single 200 mg dose of pralsetinib was administered orally alone and in combination with cyclosporine with a 9-day washout between treatments. Co-administration with cyclosporine resulted in a clinically relevant increase in pralsetinib maximum plasma concentration (Cmax) and area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞) with associated geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of 148% (109, 201) and 181% (136, 241), respectively. These findings provide insight into concomitant dosing of pralsetinib with inhibitors of P-gp given the increases in pralsetinib exposure observed when administered with cyclosporine. Based on these results, co-administration of pralsetinib with P-gp inhibitors is not recommended. In the event that co-administration cannot be avoided, it is recommended that the dose of pralsetinib be reduced.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ciclosporina
/
Interações Medicamentosas
/
Voluntários Saudáveis
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article