title: Effects of Pluronic F68 and Labrasol on the intestinal absorption and pharmacokinetics of rifampicin in rats.
abstract: The aim of this study was to investigate the effects of Pluronic F68 and Labrasol on the intestinal absorption and pharmacokinetics of rifampicin. Intestinal permeability of rifampicin with or without excipients was evaluated by an in situ single-pass perfusion method. A high-performance liquid chromatographic method was applied to study the pharmacokinetics of rifampicin with or without excipients. Labrasol or Pluronic F68 (0.1% and 0.05%, v/v), co-perfused with rifampicin (60 μg/mL), significantly increased in situ permeability. Similarly, verapamil (a typical P-gp inhibitor) also increased in situ permeability, but to a lesser extent. In vivo, the oral administration of rifampicin with or without Pluronic F68, Labrasol or verapamil resulted in statistically significant effect on t(1/2) (4.83 to 7.75, 6.42 and 7.46 h) and total body clearance (0.46 to 0.26, 0.28, 0.24 L/h/kg). In addition, Pluronic F68, Labrasol and verapamil produced minor changes in AUC(0-t), which improved 1.55-, 1.54-, and 1.73-fold in comparison to control group, respectively. These results showed that Labrasol and Pluronic F68 might inhibit the function of P-gp in the intestine, thereby increasing intestinal absorption and changing the pharmacokinetic parameters of rifampicin. Therefore, excipient selection is an important factor to consider in rational formulation design.
authors.affiliation: College of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wei
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Ma
authors.forename: Xin'an
authors.initials: X
authors.lastname: Wu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000818:Animals; D000904:Antibiotics, Antitubercular / Q000097:blood / Q000493:pharmacokinetics*; D004339:Drug Compounding; D045703:Emulsifying Agents / Q000737:chemistry / Q000494:pharmacology; D005079:Excipients / Q000737:chemistry* / Q000494:pharmacology; D005989:Glycerides; D006207:Half-Life; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D049990:Membrane Transport Modulators / Q000737:chemistry / Q000494:pharmacology; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009930:Organic Chemicals / Q000737:chemistry / Q000494:pharmacology; D010477:Perfusion; D010539:Permeability / Q000187:drug effects; D020442:Poloxamer / Q000737:chemistry* / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000097:blood / Q000493:pharmacokinetics*; D013501:Surface-Active Agents / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000904:Antibiotics, Antitubercular; D045703:Emulsifying Agents; D005079:Excipients; D005989:Glycerides; D049990:Membrane Transport Modulators; D009930:Organic Chemicals; D013501:Surface-Active Agents; C440220:Labrasol; D020442:Poloxamer; D012293:Rifampin