Corroboration of naringin effects on the intestinal absorption and pharmacokinetic behavior of candesartan cilexetil solid dispersions using in-situ rat models

Abstract

Objective: The aim of this study was to corroborate the effects of naringin, a P-glycoprotein inhibitor, on the intestinal absorption and pharmacokinetics of candesartan (CDS) from candesartan cilexetil (CAN) solid dispersions using in-situ rat models.

Materials and methods: Intestinal transport and absorption studies were examined by in-situ single pass perfusion and closed-loop models. We evaluated the intestinal membrane damage in the presence of naringin by measuring the release of protein and alkaline phosphatase (ALP).

Results and discussion: We noticed 1.47-fold increase in P_eff of CDS from freeze-dried CAN-loaded solid dispersions with naringin (15 mg/kg, w/w) when compared with freeze-dried solid dispersion without naringin using in-situ single pass intestinal perfusion model. However, no intestinal membrane damage was observed in the presence of naringin. Our findings from in-situ closed-loop pharmacokinetic studies showed 1.34-fold increase in AUC with elevated C_max and shortened t_max for freeze-dried solid dispersion with naringin as compared to freeze-dried solid dispersion without naringin.

Conclusion: This study demonstrated that increased solubilization (favored by freeze-dried solid dispersion) and efflux pump inhibition (using naringin), the relative bioavailability of CDS can be increased, suggesting an alternative potential for improving oral bioavailability of CAN.

• Candesartan
• naringin
• oral bioavailability
• P-gp
• solid dispersions

Declaration of interest

The authors report no declarations of interest.