Oral Bioavailability and Enterohepatic Recirculation of Otilonium Bromide in Rats

• Published in: Archives of pharmacal research Vol. 31; no. 1; pp. 117 - 124
• Main Authors: 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
• Format: Journal Article
• Language: Korean
• Published: 2008
• Subjects: Enterohepatic recirculation; Otilonium; Bioavailability; Pharmacokinetics
• ISSN: 0253-6269; 1976-3786

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, $V_z$ and AUC were $7.9\;{\pm}\;1.9\;h,\;8.7\;{\pm}\;3.1$ mL/min/kg, $5.7\;{\pm}\;1.4$ L/kg and $2,088\;{\pm}\;676\;ng{\cdot}h/mL$, 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 $11.6\;{\pm}\;3.0$ and $3.1\;{\pm}\;0.7$%, respectively. Upon oral administration to non-BDC rats (20 mg/kg as otilonium), $t_{1/2},\;C_{max},\; T_{max}$ and AUC were $6.4\;{\pm}\;1.3\;h,\;182.8\;{\pm}\;44.6\;ng/mL,\; 1.9\;{\pm}\;1.6\;h$ and $579\;{\pm}\;113\;ng{\cdot}h/mL$, 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.