Effect of renal ischaemia/reperfusion-induced acute kidney injury on pharmacokinetics of midazolam in rats.
J Pharm Pharmacol
; 71(12): 1792-1799, 2019 Dec.
Article
en En
| MEDLINE
| ID: mdl-31579949
ABSTRACT
OBJECTIVES:
This study aimed to investigate the effects of renal ischaemia/reperfusion (I/R)-induced acute kidney injury (AKI) on the distribution of midazolam (MDZ), a probe drug for cytochrome P450 3A (CYP3A) activity.METHODS:
We established an AKI model inducing ischaemia of both renal pedicles for 60 min followed by 24-h reperfusion. MDZ was administered intravenously (i.v.) to the rats via the jugular vein, and then, blood samples were collected to determine the plasma concentration of MDZ. KEYFINDINGS:
While the plasma concentration of MDZ after i.v. administration was decreased in the I/R rats, the tissue concentration was not altered. In addition, the tissue-to-plasma (T/P) ratio of MDZ was increased in the I/R rats. The unbound fraction of MDZ and the level of indoxyl sulphate (IS) in plasma were elevated in the I/R rats. Furthermore, the unbound fraction of MDZ was significantly increased by the addition of IS.CONCLUSIONS:
These results indicated that the displacement of albumin-bound MDZ by IS changed the unbound fraction of MDZ and elevated the T/P ratio of MDZ in I/R rats.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Midazolam
/
Daño por Reperfusión
/
Citocromo P-450 CYP3A
/
Lesión Renal Aguda
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Pharm Pharmacol
Año:
2019
Tipo del documento:
Article