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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Pharmacokinetic-pharmacodynamic contributions to the convulsant activity of fluoroquinolones in rats.

The in vivo convulsant activities in rats of five representative fluoroquinolones (FQs), norfloxacin, enoxacin, sparfloxacin, fleroxacin, and pefloxacin, were compared. The experimental approach allowed distinction between the drugs' ability to reach the pharmacological receptors at the level of the central nervous system (pharmacokinetic contribution) and their ability to interact with these receptors (pharmacodynamic contribution). The presence of a methyl group on the piperazine moiety decreased the pharmacodynamic contribution to the convulsant activity by severalfold, and the ratios of concentrations of the FQs in cerebrospinal fluid (CSF) to concentrations of unbound FQs in plasma varied from about 5 to 75% as a function of lipophilicity. Interestingly, FQs with the highest intrinsic convulsant activities had the lowest levels of diffusion in CSF and vice versa. This in vivo approach provides information complementary to that of in vitro experiments and should be recommended for early preclinical assessment of a new FQ's epileptogenic risk.[1]

References

  1. Pharmacokinetic-pharmacodynamic contributions to the convulsant activity of fluoroquinolones in rats. Delon, A., Bouquet, S., Huguet, F., Brunet, V., Courtois, P., Couet, W. Antimicrob. Agents Chemother. (1999) [Pubmed]
 
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