In-situ absorption, protein binding and pharmacokinetic studies of S002-853, a novel antidiabetic and antidyslipidaemic flavone derivative in rats.
OBJECTIVE
The aim of the study was to investigate the in-situ absorption kinetics, plasma protein binding and pharmacokinetic characteristics of a novel synthetic flavone derivative, S002-853, which shows pronounced antidiabetic and antidyslipidaemic activity.


METHODS
Quantification of S002-853 in plasma was performed by the LC-MS/MS method and in-situ sample analysis was carried out by the HPLC-UV method.


RESULTS
The absorption rate constant was 0.274/h in a mild alkaline environment, which S002-853 experiences in the intestine following oral dose administration. Plasma protein binding was found to be 26.37 +/- 2.58% at a concentration of 1 microg/ml. The pharmacokinetic parameters were determined in male rats after administration of a single 40 mg/kg oral dose and 10 mg/kg intravenous dose. The peak plasma concentration (C(max)) was found to be 60.93 ng/ml at 8 h after oral administration. Irregular concentration-time profiles with secondary peaks were observed after oral dose administration. The elimination half-life of the compound was 19.56 h and 16.30 h after oral and intravenous doses, respectively. Comparison of the AUC after oral and intravenous dosing of S002-853 indicates that only about 29.48% (bioavailability) of the oral dose reaches the systemic circulation.


CONCLUSIONS
In-situ study of S002-853 shows slow absorption from the gastrointestinal tract. S002-853 also shows low plasma protein binding. The pharmacokinetic parameters after oral and intravenous dose reveal low oral bioavailability and high mean residence time.
Gautam
Nagsen
N
Pharmacokinetics & Metabolism Division, Central Drug Research Institute, CSIR, Lucknow, India.
Kushwaha
Hari Narayan
HN
Pratap
Ram
R
Singh
Shio Kumar
SK
D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D047309:Flavones / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D006207:Half-Life; D007004:Hypoglycemic Agents / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D000960:Hypolipidemic Agents / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D010936:Plant Extracts / Q000138:chemical synthesis*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D027842:Syzygium / Q000737:chemistry*
D047309:Flavones; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D010936:Plant Extracts; C555326:S002-853 compound