Concurrent administration with multivalent metal cation preparations or polycationic polymer preparations inhibits the absorption of raltegravir via its chelation.
J Pharm Pharmacol
; 72(10): 1361-1369, 2020 Oct.
Article
en En
| MEDLINE
| ID: mdl-32657432
OBJECTIVES: Raltegravir (RAL) that can form chelates with multivalent metal cations shows lateral interactions with multivalent metal cation and polycationic polymer. We investigated the interactions of RAL with multivalent metal cation preparations, Al(OH)3 and LaCO3 , and polycationic polymer preparations, bixalomer (Bxl) and sevelamer (Svl). METHODS: Immediately before the oral administration of 40 mg/kg RAL, the rats were administered orally with the vehicle, Al(OH)3 , LaCO3 , Bxl, or Svl, and the time course of RAL serum concentration was followed. The in vitro binding affinity of RAL with multivalent metal cation and polycationic polymer was also evaluated using isothermal titration calorimetry (ITC). RESULTS: When Al(OH)3 , LaCO3 , Bxl, or Svl was concomitantly administered with RAL, the maximum concentration and area under the curve were significantly lower than those when RAL was administered alone. ITC showed the interaction of RAL with Al(OH)3 as an enthalpy-driven reaction and its interactions with LaCO3 and Bxl as entropy-enthalpy mixed reactions. CONCLUSIONS: The interaction of RAL with Al(OH)3 , LaCO3, Bxl, or Svl can inhibit RAL absorption into the gastrointestinal tract, and thus, the multivalent metal cation and polycationic polymer are the modifying factors that can affect RAL pharmacokinetics.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polímeros
/
Quelantes
/
Absorción Gastrointestinal
/
Raltegravir Potásico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Pharm Pharmacol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido