Bioavailability enhancement of a BCS IV compound via an amorphous combination product containing ritonavir.
J Pharm Pharmacol
; 68(5): 678-91, 2016 May.
Article
en En
| MEDLINE
| ID: mdl-26454138
ABSTRACT
OBJECTIVES:
To evaluate the effect of ritonavir (RTV) co-administration on the bioavailability of an amorphous dispersion of acetyl-11-keto-beta-boswellic acid (AKBA) and to develop a pharmaceutically acceptable AKBA-RTV combination tablet.METHODS:
A pharmacokinetic (PK) study in rats was conducted to evaluate the influence of RTV co-administration on the oral bioavailability of an AKBA amorphous dispersion. KinetiSol was utilized to enable production of an improved RTV formulation that facilitated the development of an AKBA-RTV combination tablet. Following in-vitro characterization, the PK performance of the tablets was evaluated in male beagles. KEYFINDINGS:
Co-administration of RTV increased oral absorption of AKBA by about fourfold over the AKBA dispersion alone and approximately 24-fold over the pure compound. The improved RTV amorphous dispersion exhibited similar purity and neutral-phase dissolution to Norvir. The AKBA-RTV combination tablets yielded a substantial increase in AKBA's bioavailability in dogs.CONCLUSIONS:
Oral absorption of AKBA is substantially limited by intestinal CYP3A activity and poor aqueous solubility. Consequently, AKBA's oral bioavailability is maximized by administration from a supersaturating formulation in conjunction with a CYP3A inhibitor. The AKBA-RTV combination tablet presented herein represents a breakthrough in the oral delivery of the compound facilitating future use as a drug therapy for broad spectrum cancer treatment.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Triterpenos
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Ritonavir
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Citocromo P-450 CYP3A
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Inhibidores del Citocromo P-450 CYP3A
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Intestinos
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Antineoplásicos Fitogénicos
Límite:
Animals
Idioma:
En
Revista:
J Pharm Pharmacol
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos