title: Significantly improved oral uptake of amikacin in FVB mice in the presence of CRL-1605 copolymer.
abstract: Amikacin is an aminoglycoside which is used in the treatment of infection from gram negative bacteria. Amikacin is also used synergistically with penicillin against gram positive cocci. Amikacin cannot be delivered orally probably due to efflux of drug by P-glycoprotein pump in the brush border of intestine. We studied the possibility of delivering amikacin orally in mice using a copolymer (CRL-1605) as a vehicle. This copolymer inhibits P-glycoprotein pump. Two different doses of amikacin were used (500 mg/kg and 100 mg/kg). The concentration of polymer used was 132 mg/kg. The liquid formulation was fed to mice by gavage and serum amikacin concentrations were estimated after one hour and two hours using fluorescence polarization immunoassay. We observed a two fold increase in serum amikacin concentration when amikacin was orally delivered in the presence of CRL-1605 compared to controls (amikacin alone). We conclude that gastrointestinal absorption of amikacin is significantly increased in the presence of CRL-1605 in mice.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, 77030, USA.
authors.forename: C
authors.initials: C
authors.lastname: Jagannath
authors.forename: A
authors.initials: A
authors.lastname: Wells
authors.forename: M
authors.initials: M
authors.lastname: Mshvildadze
authors.forename: M
authors.initials: M
authors.lastname: Olsen
authors.forename: E
authors.initials: E
authors.lastname: Sepulveda
authors.forename: M
authors.initials: M
authors.lastname: Emanuele
authors.forename: R L
authors.initials: RL
authors.lastname: Hunter
authors.forename: A
authors.initials: A
authors.lastname: Dasgupta
mesh_terms: D000284:Administration, Oral; D000583:Amikacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D004852:Epoxy Compounds; D005027:Ethylene Oxide; D005260:Female; D007408:Intestinal Absorption; D051379:Mice; D014677:Pharmaceutical Vehicles; D013501:Surface-Active Agents / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004852:Epoxy Compounds; D014677:Pharmaceutical Vehicles; D013501:Surface-Active Agents; D000583:Amikacin; D005027:Ethylene Oxide; C009068:propylene oxide