Automated analytical systems for drug development studies. Part IV. A microdialysis system to study the partitioning of lomefloxacin across an erythrocyte membrane in vitro.
An automated system utilizing microdialysis sampling, intermittent dosing, and liquid chromatographic analysis was assembled in order to study the partitioning of lomefloxacin, a fluoroquinolone antimicrobial, into human erythrocytes in vitro. The apparent erythrocyte:buffer partition coefficient was found to be approximately 2.0 with this system and by a manual method. The value was concentration-dependent; lower partition coefficients were observed at lomefloxacin concentrations less than 1 microgram ml-1. At all concentrations, values obtained by microdialysis were statistically indistinguishable from those obtained by a conventional manual method. The results indicate that erythrocyte partition coefficients can be measured successfully with the microdialysis system. Furthermore, microdialysis sampling eliminates the tedious methodology associated with traditional erythrocyte partitioning studies, including sample clean-up. Due to automated intermittent dosing and on-line LC analysis, the system operates unattended.
Knaub
S R
SR
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045, USA.
Chang
M F
MF
Lunte
C E
CE
Topp
E M
EM
Riley
C M
CM
D000328:Adult; D000890:Anti-Infective Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D001322:Autoanalysis; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002853:Chromatography, Liquid; D004910:Erythrocyte Membrane / Q000378:metabolism*; D024841:Fluoroquinolones; D006801:Humans; D066298:In Vitro Techniques; D017551:Microdialysis / Q000295:instrumentation*; D015363:Quinolones / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C053091:lomefloxacin