In situ absorption and protein binding characteristics of CDRI-85/92, an antiulcer pharmacophore.
CDRI-85/92, a new antiulcer drug, acts as a proton pump inhibitor arresting the secretion of acid in the stomach. The absorption kinetics of CDRI-85/92 was evaluated in situ using rat intestinal recirculation perfusion method. The experiment was conducted at pH 2.6 and 7.4 representing the acidic and the mild alkaline environment, which the drug experiences through the GIT during oral treatment. The rate of absorption was the same (0.12h(-1)) at pH 2.6 and 7.4, thus suggesting equal absorption profile of the CDRI-85/92 throughout the GIT irrespective of the pH. Equal rates of absorption can also be correlated with the presence of acidic and basic groups in the structure of CDRI-85/92. Protein binding studies of CDRI-85/92 using ultrafiltration were conducted in vitro and in vivo. Protein binding was found to be in the range of 31.49-32.91% both in in vitro and in vivo (employing 5-min post dose samples of rat serum after 20 mgkg(-1) i.v. treatment of CDRI-85/92). The binding was found to be linear in the concentration range of 156.25-2000 ngml(-1) (r(2)>0.99).
Srivastava
Pratima
P
Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Chattar Manzil Palace, Post Box 173, Lucknow 226001, India.
Gupta
R C
RC
D000042:Absorption; D000818:Animals; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics*; D008297:Male; D010080:Oxazoles / Q000493:pharmacokinetics*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley
D000897:Anti-Ulcer Agents; C452083:CDRI-85-92; D010080:Oxazoles