title: Pharmacokinetics of the proton pump inhibitor CDRI-85/92 and its ester prodrug, a new H+/K(+)-ATPase inhibitor with anti-ulcer activities, after oral doses in rats.
abstract: 5-Styryl-4,5-cis-1,3-oxazole-2-one-4-carboxylic acid (CDRI-85/92) is a new proton pump inhibitor presently in advanced stage of preclinical trials as antiulcer pharmacophore. Since proton pump inhibitors are prodrugs requiring activation in acid environment, an ester prodrug of CDRI-85/92 was also synthesized. In view of the importance, a pharmacokinetic study of CDRI-85/92 and its ester prodrug was conducted after oral doses in rats. Following a 20 mg/kg oral dose of CDRI-85/92, the compound was detectable in the serum samples up to 24 h with a maximum serum concentration (C(max)) of 1838.40 +/- 101.16 ng/ml at 1.5 h and an elimination half-life of 4.96 h, whereas, multiple C(max) values of CDRI-85/92 were observed with oral doses (equivalent to 20 mg/kg of CDRI-85/92) of the ester prodrug of the compound. All the three C(max) values of the compound were lower than that after oral dose of CDRI-85/92. The compound was eliminated slowly from serum with an elimination half-life of 5.14 h. Moreover, the systemic availability of CDRI-85/92 also decreased from 6111 to 3463 ng x h/ml after the ester prodrug administration. The decrease in systemic availability of CDRI-85/92 could be due to its higher clearance after its ester prodrug administration.
authors.affiliation: Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Lucknow, India. jlalcdri@rediffmail.com
authors.forename: Jawahar
authors.initials: J
authors.lastname: Lal
authors.forename: Shailendra Kumar
authors.initials: SK
authors.lastname: Pandey
authors.forename: Dinesh Kumar
authors.initials: DK
authors.lastname: Dikshit
authors.forename: Ram Chandra
authors.initials: RC
authors.lastname: Gupta
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D002138:Calibration; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D008297:Male; D010080:Oxazoles / Q000493:pharmacokinetics*; D019999:Pharmaceutical Solutions; D011355:Prodrugs / Q000493:pharmacokinetics*; D054328:Proton Pump Inhibitors / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D013535:Suspensions
chemical_list: D000897:Anti-Ulcer Agents; C452083:CDRI-85-92; D010080:Oxazoles; D019999:Pharmaceutical Solutions; D011355:Prodrugs; D054328:Proton Pump Inhibitors; D013535:Suspensions