title: Diglyceride prodrug strategy for enhancing the bioavailability of norfloxacin.
abstract: Prodrug approach using diglyceride as a promoiety is a promising strategy to improve bioavailability of poorly absorbed drugs and the same was explored in the present work to improve oral bioavailability of norfloxacin; a second generation fluoroquinolone antibacterial. The prodrug was synthesized by standard procedures using dipalmitine as a carrier and the structure was confirmed by spectral analysis. Higher LogP indicated improved lipophilicity. The ester linkage between norfloxacin and dipalmitine would be susceptible to hydrolysis by lipases to release the parent drug and carrier in the body. In vivo kinetic studies in rats indicated 53% release of norfloxacin in plasma at the end of 8h. The prodrug exhibited improved pharmacological profile than the parent compound at equimolar dose that indirectly indicated improved bioavailability.
authors.affiliation: Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune, Maharashtra, India. suneeladhaneshwar@rediffmail.com
authors.forename: Suneela
authors.initials: S
authors.lastname: Dhaneshwar
authors.forename: Kunal
authors.initials: K
authors.lastname: Tewari
authors.forename: Sonali
authors.initials: S
authors.lastname: Joshi
authors.forename: Dhanashree
authors.initials: D
authors.lastname: Godbole
authors.forename: Pinaki
authors.initials: P
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D055162:Biocatalysis; D001682:Biological Availability; D004075:Diglycerides / Q000737:chemistry / Q000494:pharmacology*; D006868:Hydrolysis; D007700:Kinetics; D008049:Lipase / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009643:Norfloxacin / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D004075:Diglycerides; D011355:Prodrugs; D008049:Lipase; D009643:Norfloxacin