Determination of the in vivo post-antibiotic effects of ciprofloxacin and rifampicin.
A modified rabbit meningitis model is described for determining the PAE in vivo, which utilised a self-standing device for repeatedly sampling pure CSF. The model allowed the PAEs of ciprofloxacin and rifampicin on Escherichia coli ATCC 25922 to be determined following PAE induction in vitro, or in vivo in CSF after intrathecal injection or during the last 1.5 h of a 7 h iv continuous infusion. The estimated volumes of distribution of ciprofloxacin and rifampicin in CSF were 0.68 +/- 0.24 mL and 0.74 +/- 0.04 mL, respectively, and the terminal elimination half lives were 1.8 +/- 0.5 h and 2.2 +/- 0.3 h, respectively. PAEs of approximately 2 h were obtained in vivo and in vitro after exposing E. coli to 3 x MIC of ciprofloxacin in vitro and to 1 x MIC of drug in vivo. When the organism was exposed to rapidly declining concentrations in vivo, only a minimal PAE was observed for both antibiotics. Moreover, a PAE of 3.1 +/- 1.3 h of rifampicin was obtained in vivo, being smaller than the 4.8 h PAE observed in vitro, which might be explained by the binding of 45 +/- 6.5% rifampicin to proteins in the CSF.
Meng
X
X
School of Pharmacy, University of Connecticut, Storrs, USA.
Pei
Y
Y
Nightingale
C H
CH
Quintiliani
R
R
D000818:Animals; D000890:Anti-Infective Agents / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D000904:Antibiotics, Antitubercular / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects*; D005260:Female; D007262:Infusions, Intravenous; D007278:Injections, Spinal; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D012293:Rifampin / Q000134:cerebrospinal fluid / Q000494:pharmacology*
D000890:Anti-Infective Agents; D000904:Antibiotics, Antitubercular; D002939:Ciprofloxacin; D012293:Rifampin