Determination and pharmacokinetic study of unbound cefepime in rat bile by liquid chromatography with on-line microdialysis.
Biliary excretion and intestinal reabsorption in enterohepatic circulation play major dispositional roles for some drugs. To investigate biliary excretion of drug, we inserted a microdialysis probe into the bile common duct of rat between the liver and the duodenum. In order to avoid the obstruction of bile fluid or bile salt waste, a shunt linear microdialysis probe was used for simultaneous and continuous sampling following intravenous administration of cefepime (50 mg/kg, i.v.). Separation and quantitation of cefepime in the dialysates were achieved using a LiChrosorb RP-18 column (Merck; 250x4.6 mm I.D., particle size 5 microm) maintained at ambient temperature. Samples were eluted with a mobile phase containing 100 mM monosodium phosphoric acid (pH 3.0)-methanol (87:13, v/v). The UV detector wavelength was set at 270 nm. The result indicates that the elimination half-life of cefepime in bile was 64.01+/-9.32 min. This study also served as an example for the microdialysis application in the biliary excretion study of drug.
Chang
Y L
YL
Institute of Pharmacology, National Yang-Ming University, and Veterans General Hospital-Taipei, Taiwan.
Chou
M H
MH
Lin
M F
MF
Chen
C F
CF
Tsai
T H
TH
D000818:Animals; D019540:Area Under Curve; D001646:Bile / Q000737:chemistry*; D000077723:Cefepime; D002511:Cephalosporins / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet
D002511:Cephalosporins; D000077723:Cefepime