|
KMID : 0359319950350040815
|
|
Korean Journal of Veterinary Research
1995 Volume.35 No. 4 p.815 ~ p.822
|
|
|
Toxicokinetics of rifapentine in beagle dogs
|
|
Shin Ho-Chul
Lee Hye-Suk
Cha Shin-Woo
Han Sang-Seop
Roh Jung-Koo
Kim Jin-Seok
Lee Won-Chang
|
|
|
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(Cmat), 28.90㎍/ml; maximum concentration time(Tmat), 3.7hr; elimination half-life(t{1/2}, 4.7hr; area under the curve(AUC), 339.0㎍·hr/ml; volume of disiribution/bioavailability (Vd/F), 0.21 l/kg; lag time, 24min; absorption rate constant(kα), 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_mat, 34.40㎍/ml; T_{mat}, 2.6hr; t_{1/2}, 6.7hr; AUC, 391.3㎍·hr/ml; Vd/F, 0.291/kg; kα, 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 2.2~25.2㎍/ml, and 10.6~125.2㎍/ml at the doses of 10 and 50mg/kg/day, respectively.
|
|
|
KEYWORD
|
|
|
toxicokinetics , rifapentine , beagle dogs
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|