title: Absorption enhancement studies of clopidogrel hydrogen sulphate in rat everted gut sacs.
abstract: OBJECTIVE
  Clopidogrel, a thienopyridine antiplatelet agent, is a poor aqueous soluble compound and a P-glycoprotein (P-gp) efflux pump substrate. These two factors are responsible for its incomplete intestinal absorption. In this study, we have attempted to enhance the absorption of clopidogrel by improving its solubility and by inhibiting intestinal P-gp activity.
  
  
  METHODS
  Solubility enhancement was achieved by preparing solid dispersions. Quinidine and naringin were selected as P-gp inhibitors, whilst tartaric acid was selected as the intestinal absorption enhancer. Absorption studies were performed using the everted gut sac model prepared from rat jejunum. The determination of clopidogrel was performed by high performance liquid chromatography.
  
  
  RESULTS
  We noticed an enhancement of clopidogrel absorption by improving its solubility or by inhibiting the P-gp activity. The greatest results were obtained for solid dispersions in the presence of P-gp inhibitors at their highest concentrations, with an absorption improvement of 3.41- and 3.91-fold for naringin (15mg/kg) and quinidine (200µm), respectively. However, no clopidogrel absorption enhancement occurred in the presence of tartaric acid.
  
  
  CONCLUSIONS
  Naringin, a natural compound which has no undesirable side effects as compared with quinidine, could be used as a pharmaceutical excipient in the presence of clopidogrel solid dispersions to increase clopidogrel intestinal absorption and therefore its oral bioavailability.
authors.affiliation: Laboratory of Galenic Pharmacy, University of Monastir, Monastir, Tunisia. lassoued98@yahoo.fr
authors.forename: Mohamed Ali
authors.initials: MA
authors.lastname: Lassoued
authors.forename: Souad
authors.initials: S
authors.lastname: Sfar
authors.forename: Abderrahman
authors.initials: A
authors.lastname: Bouraoui
authors.forename: Fathia
authors.initials: F
authors.lastname: Khemiss
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D005079:Excipients / Q000008:administration & dosage / Q000494:pharmacology*; D044950:Flavanones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011802:Quinidine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013644:Tartrates / Q000008:administration & dosage / Q000494:pharmacology; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005079:Excipients; D044950:Flavanones; D010975:Platelet Aggregation Inhibitors; D013644:Tartrates; D000077144:Clopidogrel; D011802:Quinidine; C005274:naringin; D013988:Ticlopidine; C029768:tartaric acid