Toxicokinetics of rifapentine in beagle dogs |
Ho-chul Shin1, Hye-suk Lee1, Shin-woo Cha1, Sang-seop Han1, Jung-ku Roh1, Jin-suk Kim2, Won-chang Lee2 |
1Toxicology Research Center, Korea Research Institute of Chemical Technology 2Department of Veterinary Medicine, Konkuk University |
Beagle dog에 있어서 rifapentine의 독성동태연구 |
신호철1, 이혜숙1, 차신우1, 한상섭1, 노정구1, 김진석2, 이원창2 |
1한국화학연구소 안전성연구센터 2건국대학교 수의학과 |
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Abstract |
The toxicokinetics of rifapentine was studied after an oral administration to beagle dogs. High-performance liquid chromatography(HPLC) using column-switching technique was performed to determine the serum concentrations of rifapentine. The pharmacokinetic profiles of rifapentine were analysed using one-compartment open model. Following a single oral administration of 10mg/kg, pharmacokinetic parameters were determined as follows: maximum serum concentration($C_{max}$), $28.90{mu}g/ml$; maximum concentration time($T_{max}$), 3.7hr; elimination half-life($t_{1/2}$, 4.7hr; area under the curve(AUC), $339.0{mu}g{cdot}hr/ml$; volume of disiribution/bioavailability (Vd/F), 0.21 l/kg; lag time, 24min; absorption rate constant($k_a$), $0.445hr^{-1}$; elimination rate constant($k_{el}$), $0.148hr^{-1}$. After 6 month multiple oral doses of 10mg/kg/day, parameters were as follows: $C_{max}$, $34.40{mu}g/ml$; $T_{max}$, 2.6hr; $t_{1/2}$, 6.7hr; AUC, $391.3{mu}g{cdot}hr/ml$; Vd/F, 0.291/kg; $k_a$, $0.976hr^{-1}$; $k_{el}$, $0.104hr^{-1}$. The consistant kinetic parameters after a single and multiple oral administration show that there was no accumulation of rifapentine after 6 month oral administration. We also simulated the concentration of rifapentine after oral multiple administration of 10 and 50mg/kg/ day, based on the parameters obtained form the single administration. The measured serum concentrations of rifapentine were well fitted to the simulated results. The simulated results show that rifapentine readily reaches to steady-state after about 3 doses and the steady-state serum concentrations($C_{ss}$) are fluctuated in between $2.2{sim}25.2{mu}g/ml$, and $10.6{sim}125.2{mu}g/ml$ at the doses of 10 and 50mg/kg/day, respectively. |
Key Words:
toxicokinetics, rifapentine, beagle dogs |
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