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Arzneimittelforschung 2009; 59(11): 564-570
DOI: 10.1055/s-0031-1296445
Antiemetics · Gastrointestinal Drugs · Urologic Drugs
Editio Cantor Verlag Aulendorf (Germany)

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

Jawahar Lal
1   Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Lucknow, (India)
,
Shailendra Kumar Pandey
1   Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Lucknow, (India)
,
Dinesh Kumar Dikshit
2   Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow, (India)
,
Ram Chandra Gupta
1   Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Lucknow, (India)
› Author Affiliations
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Publication History

Publication Date:
13 December 2011 (online)

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Abstract

5-Styryl-4,5-cis-1,3-oxazole-2-one-4-car-boxylic 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 (Cmax) of 1 838.40 ± 101.16 ng/ml at 1.5 h and an elimination half-life of 4.96 h, whereas, multiple Cmax 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 Cmax 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 3 463 ng · 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.

Key words

CDRI-85/92, HPLC, pharmacokinetics, prodrug, rat - Proton pump inhibitor - 5-Styryl-4,5-cis-1,3-oxazole-2-one-4-carboxylic acid
 

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