title: Pharmacokinetic Studies of Oxathio-Heterocycle Fused Chalcones.
abstract: OBJECTIVE
  Chalcone constitutes one of the most used molecular frameworks in medicinal chemistry and its derivatives exhibit a broad spectrum of biological activities. Low absolute bioavailability, poor distribution, intensive metabolism and elimination of chalcones are the main problems in designing new drugs based on their structure. One of the fundamental steps in evaluation of drug candidates is a comparative analysis of pharmacokinetic parameters. The aim of the studies was the pharmacokinetic characterization of the selected oxathio-heterocycle fused chalcones.
  
  
  METHODS
  The pharmacokinetic parameters of 19 compounds were reported. The analyzed chalcones were examined after a single intravenous administration to forty 7-week-old mature male rats of Wistar stock. Pharmacokinetic analysis was performed independently using SHAM (slopes, highest, amounts, and moments) and the two-compartment model. Basic physiochemical parameters were calculated. The bioanalytical methods were validated in terms of repeatability, linearity, accuracy, precision, and selectivity.
  
  
  RESULTS
  The pharmacokinetics of the examined group of chalcones are compatible with the two-compartment model. The physicochemical characteristics of this group are quite homogeneous. The kinetics of the examined chalcones are indicative of a distribution to the tissue compartment with the predominance of a rate constant from central to peripheral compartments (k12) over the rate constant from peripheral to central compartments (k21). The elimination from the central compartment (k10) is higher than the transfer from the central compartment to the tissues (k10> k12) in almost all examined cases.
  
  
  CONCLUSIONS
  The presented group of compounds may form a starting point for studies into drugs treating autoimmune diseases of the gastro-intestinal tract.
authors.affiliation: P.F.O. Vetos-Farma sp. z o. o., ul. Dzierżoniowska 21, 58-260, Bielawa, Poland. krystyna.okoniewska@vetos-farma.com.pl.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Okoniewska
authors.affiliation: Department of Chemical Technology of Drugs, Medical University of Gdansk, 80-416, Gdańsk, Poland.
authors.forename: Marek T
authors.initials: MT
authors.lastname: Konieczny
authors.affiliation: Biovico sp. z o. o., ul. Hryniewickiego 6b/135, 81-340, Gdynia, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Lemke
authors.affiliation: Polpharma Biologics, ul. Trzy Lipy 3, 80-172, Gdańsk, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Grabowski
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D047188:Chalcones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000068598:Data Accuracy; D008297:Male; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results
chemical_list: D047188:Chalcones
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