title: Evaluation of an intracellular pharmacokinetic in vitro infection model as a tool to assess tuberculosis therapy.
abstract: In vitro intracellular infection models have been used to evaluate drug therapy against Mycobacterium tuberculosis; however, they do not simulate human pharmacokinetics. This study demonstrates the intracellular and extracellular killing activity of antimycobacterial drugs in a pharmacokinetic intracellular in vitro model. The pharmacokinetic parameters of levofloxacin, rifampicin and isoniazid were controlled in the central chamber; drug passively diffused into the cell culture inserts and then into the macrophages. In the pharmacokinetic model, the rates of killing observed were faster than other in vitro methods and allowed for a higher initial inoculum to be utilised. The pharmacokinetic model more closely mimics in vivo conditions than other in vitro systems and is a new instrument for evaluating the activity of antimycobacterial agents.
authors.affiliation: The University of Toledo, College of Pharmacy #609, 2801 W. Bancroft Street, Toledo, OH 43606, USA. dcappel@utnet.utoledo.edu
authors.forename: Diane M
authors.initials: DM
authors.lastname: Cappelletty
mesh_terms: D000995:Antitubercular Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D002460:Cell Line; D006207:Half-Life; D006801:Humans; D007538:Isoniazid / Q000493:pharmacokinetics / Q000494:pharmacology; D064704:Levofloxacin; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D015242:Ofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology; D012293:Rifampin / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D064704:Levofloxacin; D015242:Ofloxacin; D007538:Isoniazid; D012293:Rifampin