title: 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.
  
  
  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).
  
  
  CONCLUSIONS
  We noticed 1.47-fold increase in Peff 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 Cmax and shortened tmax for freeze-dried solid dispersion with naringin as compared to freeze-dried solid dispersion without naringin.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Vaagdevi Institute of Pharma Sciences , Warangal, Andhra Pradesh , India .
authors.forename: Gurunath
authors.initials: G
authors.lastname: Surampalli
authors.forename: Basavaraj
authors.initials: B
authors.lastname: K Nanjwade
authors.forename: P A
authors.initials: PA
authors.lastname: Patil
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005079:Excipients / Q000737:chemistry*; D044950:Flavanones / Q000737:chemistry*; D005612:Freeze Drying; D007408:Intestinal Absorption; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D005079:Excipients; D044950:Flavanones; D013777:Tetrazoles; C005274:naringin; C077793:candesartan cilexetil
keywords: Candesartan; P-gp; naringin; oral bioavailability; solid dispersions