title: Oral bioavailability and intestinal absorption of candesartan cilexetil: role of naringin as P-glycoprotein inhibitor.
abstract: OBJECTIVE
  The aim of the study is to explore the pharmacokinetic behavior of candesartan solid dispersions prepared by different pharmaceutical interventions using P-gp inhibitor in rabbits to validate the effectiveness of naringin as a pharmaceutical excipient in enhancing the oral delivery of lipophilic candesartan cilexetil.
  
  
  METHODS
  Male albino rabbits (1-1.5 kg) were orally administered pure CAN suspensions and various candesartan solid dispersions (10 mg/kg) with and without naringin (15 mg/kg) and blood samples were collected at specified time points. CAN plasma samples were measured using HPLC.
  
  
  RESULTS
  After oral dosing of pure CAN suspension, the mean AUC0-8 h was found to be 0.14 ± 0.09 μgh/ml which was increased significantly, i.e. 0.52 ± 0.13 μgh/ml with freeze-dried solid dispersions in the presence of naringin (p < 0.01). Similarly, the mean Cmax of pure CAN suspension increased from 35.81 ± 0.13 μg/ml (without naringin) to 112.23 ± 0.13 μg/ml (freeze-dried solid dispersions with naringin) (p < 0.01). A 3.7-folds increase in apparent bioavailability was noticed with freeze-dried solid dispersions with naringin as compared to free CAN suspension administered alone.
  
  
  CONCLUSIONS
  These results are quite stimulating for further development of a clinically useful oral formulation of candesartan cilexetil based on P-gp inhibition using naringin, a natural flavonoid as a pharmaceutical excipient.
authors.affiliation: Department of Pharmacology, Vaagdevi Institute of Pharmaceutical Sciences , Warangal, Andhra Pradesh , India .
authors.forename: Surampalli
authors.initials: S
authors.lastname: Gurunath
authors.forename: Basavaraj K
authors.initials: BK
authors.lastname: Nanjwade
authors.forename: P A
authors.initials: PA
authors.lastname: Patil
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors*; D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D044950:Flavanones / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011817:Rabbits; D013777:Tetrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044950:Flavanones; D013777:Tetrazoles; C005274:naringin; C077793:candesartan cilexetil
keywords: Candesartan; P-gp inhibition; lipophilic drug; naringin; oral bioavailability