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Determination of Novel Synthetic 5HT2C Agonist KOPC20010 by Gas-Chromatography/Mass Spectrometry and its Bioavailability in Sprague-Dawley Rats
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  • Determination of Novel Synthetic 5HT2C Agonist KOPC20010 by Gas-Chromatography/Mass Spectrometry and its Bioavailability in Sprague-Dawley Rats
  • Determination of Novel Synthetic 5HT2C Agonist KOPC20010 by Gas-Chromatography/Mass Spectrometry and its Bioavailability in Sprague-Dawley Rats
저자명
Im. Hye-Yeon,Pae. Ae-Nim,Yang. Ha-Yun,Park. Woo-Kyu,Seo. Ji-Eun,Haque. Md. Mamunul,Kwon. Oh-Seung
간행물명
Journal of pharmaceutical investigation
권/호정보
2011년|41권 1호|pp.31-36 (6 pages)
발행정보
한국약제학회
파일정보
정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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기타언어초록

$5HT_{2C}$ 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.