[Tissue pharmacokinetics of antibiotics. Theoretical bases and new pharmacological approaches].
Tissue pharmacokinetics has become an important feature of our knowledge of antibiotic behavior in the human body. Serum pharmacokinetic parameters are well established for all available antimicrobial agents but do not provide a means of assessing concentrations to be achieved at the site of infection nor an evaluation of intracellular penetration and bioactivity. Studies of tissue concentrations in animal or human models would be of more clinical significance if they took into account several in vivo microbial parameters such as the intracellular location of the pathogens, their state of growth, and size of the inoculum at the infection site. When minimal inhibitory concentrations are established, there could be a significant difference between in vitro results and the in vivo conditions. Pharmacodynamic parameters offer a new approach to antibiotic bioactivity in the patient. In addition to physicochemical characteristics of antibiotics governing tissue distribution, particularly liposolubility and degree of ionisation, patient conditions should also be considered as major factors interfering with in vivo antibiotic behavior. These concerns are of particular relevance for infections involving lung tissues, cerebrospinal fluid, bones and several other sites of infection. Newer approaches in tissue pharmacology of antibiotics are in progress.
Bergogne-Bérézin
E
E
Service de Microbiologie, CHU Bichat-Claude Bernard, Paris.
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001419:Bacteria / Q000254:growth & development; D001424:Bacterial Infections / Q000503:physiopathology; D005110:Extracellular Space; D006801:Humans; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents
Pharmacocinétique tissulaire des antibiotiques. Bases théoriques et nouvelles approches pharmacologiques.