Oral bioavailability and enterohepatic recirculation of otilonium bromide in rats.
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 t(1/2), CL, Vz and AUC were 7.9 +/- 1.9 h, 8.7 +/- 3.1 mL/min/kg, 5.7 +/- 1.4 L/kg and 2,088 +/- 676 ng h/mL, 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 +/- 3.0 and 3.1 +/- 0.7%, respectively. Upon oral administration to non-BDC rats (20 mg/kg as otilonium), t(1/2), Cmax, Tmax and AUC were 6.4 +/- 1.3 h, 182.8 +/- 44.6 ng/mL, 1.9 +/- 1.6 h and 579 +/- 113 ng 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.
Shin
Beom Soo
BS
College of Pharmacy, Catholic University of Daegu, Gyeongsan-si, Gyeongbuk, Korea.
Kim
Jung Jun
JJ
Kim
John
J
Hu
Sul Ki
SK
Kim
Hyoung Jun
HJ
Hong
Seok Hyun
SH
Kim
Han Kyung
HK
Lee
Hye Suk
HS
Yoo
Sun Dong
SD
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001646:Bile / Q000378:metabolism; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004764:Enterohepatic Circulation; D006207:Half-Life; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D008297:Male; D010276:Parasympatholytics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards
D010276:Parasympatholytics; D000644:Quaternary Ammonium Compounds; C013934:octylonium