title: Application of a new high performance liquid chromatography method to the pharmacokinetics of dibudipine in rats.
abstract: OBJECTIVE
  To develop a HPLC method for assay of dibudipine in biological fluids and to study its pharmacokinetics in the rat.
  
  
  METHODS
  HPLC: 2 microl (20 microg/ml) mebudipine as internal standard, 0.2 ml NaOH 1 M and 2 ml ethyl acetate were added to 0.2 ml of rat plasma. The mixture was shaken for 10 min, centrifuged, and the supernatant was dried under nitrogen. The dissolved residue was injected to a C18 analytical column. Mobile phase flowed at 1 ml/min with a composition of methanol--water-acetonitrile (70-25-5). The eluent was monitored at 238 nm. Pharmacokinetic study: plasma samples were collected periodically after intravenous (0.5 mg/kg) or oral (10 mg/kg) administration of dibudipine to rats (n = 4/group). In addition, separate groups of animals were administered 0.5 mg/kg doses of the drug for serial collection of brain, heart, kidney and liver (n = 4/time). The concentration of the drug in tissue or plasma was assayed using the above HPLC method.
  
  
  RESULTS
  Calibration curves were linear over a concentration of 10-1000 ng/ml and CV was less than 10%. Dibudipine showed a bi-exponential decline after IV injection in the rats with a t1/2 beta of 2.5 +/- 0.5(mean +/- SE) hr. Oral bioavailability was low. Distribution of dibudipine to the examined tissues was rapid, and with the exception of the brain, the concentrations of the drug in all tissues were higher than the plasma levels
  
  
  CONCLUSIONS
  The HPLC method was simple and convenient. Moreover, it could be applied to investigations of the pharmacokinetics of dibudipine in the rat.
authors.affiliation: Razi Institute for Drug Research, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Shahab
authors.initials: S
authors.lastname: Bohlooli
authors.forename: Fariborz
authors.initials: F
authors.lastname: Keyhanfar
authors.forename: Saeed
authors.initials: S
authors.lastname: Ghiaee
authors.forename: Massoud
authors.initials: M
authors.lastname: Mahmoudian
mesh_terms: D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C110813:dibudipine; C110812:mebudipine; D009543:Nifedipine