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Study on Medicinal Chemistry of K203 in Wistar Rats and Beagle Dogs

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Abstract:

K203 is an experimental bis–pyridinium mono-aldoxime type cholinesterase reactivator of potential use in organophosphate- organophosphonate poisoning. Pharmacokinetics of K203 were examined in Wistar rats and beagle dogs using ion–pair HPLC. Serum and cerebrospinal fluid concentrations of K203 were determined using ion-pair reversedphase chromatography on octadecyl silica column. HPLC with ultraviolet detection was used for determination of serum concentration of K203 higher than 0.1 μg-mL while its low concentrations in cerebrospinal fluid required electrochemical detection (0.015 through 4 μg-mL range). In rats the serum levels of K203 followed zero order pharmacokinetics from 15 to 120 minutes post administration. Zero order pharmacokinetics was also observed in beagle dogs after low dose (15 μmol-kg) of K203 administration. High dose administration (250 μmol-kg) led to subsequent hindered elimination from both cerebrospinal fluid and serum.

Keywords: Amperometric detection; HPLC; K203; UV detection; beagle dogs; pharmacokinetics; rats; serum level

Document Type: Research Article

Publication date: May 1, 2013

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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