Effect of aluminium ion on bioavailability of levofloxacin following oral administration of cilexetil ester of levofloxacin as prodrug in rats.
Pharmazie
; 75(11): 554-558, 2020 11 01.
Article
en En
| MEDLINE
| ID: mdl-33239128
ABSTRACT
A prodrug of levofloxacin (LVFX), cilexetil ester of LVFX (LVFX-CLX), was synthesized to examine whether the prodrug can avoid chelate formation with metal cations in the gastrointestinal tract. LVFX-CLX exhibited a 10-times higher partition coefficient than LVFX. In vitro, LVFX was precipitated by 76.1% in the presence of a 10-times higher concentration of aluminium chloride (Al3+), but LVFX-CLX was not. LVFX-CLX was rapidly hydrolyzed enzymatically by rat plasma, intestinal mucosal and liver homogenates at 37 °C, but not by pancreatic enzymes and luminal fluid. The minimum inhibitory concentration values of LVFX-CLX against S. aureus, E. coli and P. aeruginosa were far higher than that of LVFX. In rats, area under the plasma concentration-time curve from zero to 4 h (AUC0-4h) of LVFX after oral administration of LVFX-CLX was 1.34-fold higher than that after LVFX, though it did not reach significance level. Co-administration of Al3+ with LVFX and LVFX-CLX in rats decreased AUC0-4h of plasma LVFX by 75% and 60%, respectively, however, the AUC0-4h of plasma LVFX after co-administration of LVFX-CLX and Al3+ was 2.2-times higher than that after co-administration of LVFX and Al3+. These results suggested that the use of LVFX-CLX may reduce the modulation of intestinal microflora caused by LVFX and the suppressive effect of Al3+ on intestinal absorption of LVFX.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_neglected_diseases
/
3_zoonosis
Asunto principal:
Aluminio
/
Levofloxacino
/
Antibacterianos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Pharmazie
Asunto de la revista:
FARMACIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón