Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
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Determination of Novel Synthetic 5HT2C Agonist KOPC20010 by Gas-Chromatography/Mass Spectrometry and its Bioavailability in Sprague-Dawley Rats

  • Im, Hye-Yeon (Doping Control Center, Korea Institute of Science and Technology (KIST)) ;
  • Pae, Ae-Nim (Neuro-Medicine Center, Korea Institute of Science and Technology (KIST)) ;
  • Yang, Ha-Yun (Neuro-Medicine Center, Korea Institute of Science and Technology (KIST)) ;
  • Park, Woo-Kyu (Pharmacology Research Center, Korea Research Institute of Chemical Technology) ;
  • Seo, Ji-Eun (Doping Control Center, Korea Institute of Science and Technology (KIST)) ;
  • Haque, Md. Mamunul (Doping Control Center, Korea Institute of Science and Technology (KIST)) ;
  • Kwon, Oh-Seung (Doping Control Center, Korea Institute of Science and Technology (KIST))
  • Received : 2011.01.26
  • Accepted : 2011.02.20
  • Published : 2011.02.20
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Abstract

$5HT_{2C}$ receptor among fourteen 5-HT subtypes plays important roles in several disorders such as depression, anxiety, epilepsy, schizophrenia and sleep disorders. The purpose of the study is to investigate pharmacokinetic parameters and bioavailability of a newly synthesized selective agonist of $5-HT_{2C}$ receptor, KOPC-20010 (KP10) in rats after intravenous and oral administration for the development of therapeutic anti-obesity agents. KP10 was administered orally (40 mg/kg) or intravenously (20 mg/kg), blood was collected via a catheter, and analyzed by GC/MSD. The calibration curve of KP10 in plasma and urine showed high linearity ($r^2$ >0.999). The retention times of KP10 in plasma and urine were 8.7 and 9.7 min, respectively. After oral administration of 40 mg/kg, pharmacokinetic parameters were calculated as follows; $C_{max}$ value was $1242.9{\pm}1195.5$ ng/mL at $1.1{\pm}0.6$ hr ($T_{max}$). $AUC_{0->24hr}$ and $AUC_{0>{\infty}}$ were $8034.2{\pm}960.7$ and $10464.1{\pm}681.5\;ng{\cdot}hr/mL$, respectively. The terminal half-life was $21.9{\pm}7.6$ hr. $AUC_{0->24hr}$ and $AUC_{0>{\infty}}$ were $4292.4{\pm}523.0$ and $6111.2{\pm}756.2\;ng{\cdot}hr/mL$, respectively, after 20 mg/kg of intravenous administration. The terminal half-life after intravenous administration was $25.1{\pm}9.4$ hr. Bioavailability of KP10 was determined to 86%. The excretion amount into the urine within 48 hr was approximately 4.7 to 6.7% of the dose administered. These data may be beneficial to the anti-obesity drug development of KP10.

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