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KMID : 0043320080310010117
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Archives of Pharmacal Research
2008 Volume.31 No. 1 p.117 ~ p.124
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Oral Bioavailability and Enterohepatic Recirculation of Otilonium Bromide in Rats
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Shin Beom-Soo
Kim Jung-Jun
Kim John
Hu Sul-Ki
Kim Hyoung-Jun
Hong Seok-Hyun
Kim Han-Kyung
Lee Hye-Suk
Yoo Sun-Dong
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Abstract
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This study was conducted to examine the oral bioavailability and the possibility of enterohepatic recirculation of otilonium bromide in rats. A sensitive LC/MS/MS assay (LLOQ 0.5 ng/mL) was developed for the determination of otilonium and applied to i.v. and oral administration studies in bile duct cannulated (BDC) and non-BDC rats. After i.v. injection to BDC rats (1 mg/kg as otilonium), average t1/2 , CL,V3 and AUC were 7.9±1.9h,8.7±3.1 mL/min/kg, 5.7±1.4 L/kg and , respectively, and these values were comparable to those found in non-BDC rats. The percentages of i.v. dose excreted unchanged in bile and urine in BDC rats were 11.6±3.1 and3.1±0.7 %, respectively. Upon oral administration to non-BDC rats (20 mg/kg as otilonium), t1/2 Cmax,Tmaxand AUC were 6.4±1.3h,182.8±44.6ng/ml,1.9±1.6h and 579±113ng.h/ml , respectively. The absolute oral bioavailability was low (1.1%), while the drug was preferentially distributed to gastrointestinal tissues. A secondary peak was observed in the serum concentration-time profiles in non-BDC rats following both i.v. and oral administration, indicating that otilonium bromide was subject to enterohepatic recirculation.
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KEYWORD
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Otilonium, Bioavailability, Enterohepatic recirculation, Pharmacokinetics
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