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KMID : 0369820110410010031
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Jorunal of Korean Pharmaceutical Sciences
2011 Volume.41 No. 1 p.31 ~ p.36
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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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Im Hye-Yeon
Pae Ae-Nim
Yang Ha-Yun
Park Woo-Kyu
Seo Ji-Eun
Haque Md. Mamunul
Kwon Oh-Seung
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Abstract
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? 5HT2C 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-HT2C 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 (r2 >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; Cmax value was 1242.9±1195.5 ng/mL at 1.1±0.6 hr (Tmax). AUC0->24hr and AUC0->∞ were 8034.2±960.7 and 10464.1±681.5 ng·hr/
mL, respectively. The terminal half-life was 21.9±7.6 hr. AUC0->24hr and AUC0->∞ were 4292.4±523.0 and 6111.2±756.2 ng·hr/mL, respectively, after 20 mg/kg of intravenous administration. The terminal half-life after intravenous administration was 25.1±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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KEYWORD
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5HT2C agonist, KOPC20010, Pharmacokinetics, Anti-obesity, Bioavailability
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