Measurement of unbound ranitidine in blood and bile of anesthetized rats using microdialysis coupled to liquid chromatography and its pharmacokinetic application

J Chromatogr A. 2005 May 6;1073(1-2):297-302. doi: 10.1016/j.chroma.2004.08.079.


To investigate the pharmacokinetics of unbound ranitidine in rat blood and bile, multiple microdialysis probes coupled to a liquid chromatographic system were developed. This study design was parallel in the following groups: the control-group of six rats received ranitidine alone (10 and 30 mg/kg, i.v.), the treated-group rats were co-administered with ranitidine and cyclosporine (P-glycoprotein (P-gp) inhibitor) or quinidine (both organic cation transport (OCT) and P-gp inhibitors) in six individual rats. Microdialysis probes were inserted into the jugular vein and the bile duct for blood and bile fluids sampling, respectively. Ranitidine in the dialysate was separated by a reversed-phase C18 column (Zorbax, 150 mm x 4.6 mm i.d.; 5 microm) maintained at ambient temperature. Samples were eluted with a mobile phase containing acetonitrile-methanol-tetrahydrofuran-20 mM K2HPO4 (pH 7.0) (24:20:10:946, v/v), and the flow rate of the mobile phase was 1 ml/min. The optimal UV detection for ranitidine was set at wavelength 315 nm. Between 20 and 30 min after drug administration (10 or 30mg/kg), the ranitidine reached the maximum concentration in the bile. The bile-to-blood distribution ratio (AUC(bile)/AUC(blood)) was 9.8 +/- 1.9 and 13.9 +/- 3.8 at the dosages of 10 and 30 mg/kg, respectively. These studies indicate that ranitidine undergoes hepatobiliary excretion which against concentration gradient from bile-to-blood. In addition, the AUC of ranitidine in bile decreased in the treatment of cyclosporine or quinidine, which suggests that the hepatobiliary excretion of ranitidine was partially regulated by P-glycoprotein or organic cation transporter.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Animals
  • Bile / chemistry*
  • Histamine H2 Antagonists / blood
  • Histamine H2 Antagonists / pharmacokinetics*
  • Male
  • Microdialysis
  • Ranitidine / blood
  • Ranitidine / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Sensitivity and Specificity


  • Histamine H2 Antagonists
  • Ranitidine