Study on the Pharmacokinetics of Arotinoid Ethylester in Beagle Dogs / 中国药房

ABSTRACT

OBJECTIVE:To study the pharmacokinetic characteristics of arotinoid ethyl ester (RO) in Beagle dogs in vivo. METHODS:18 Beagle dogs were randomly divided into high-dose,medium-dose,low-dose groups (40,20,10 mg/kg),6 in each group. Rats were intragastrically administrated related doses of RO. Blood sample 1 mL was taken after 0.5,1.0,2.0,4.0, 6.0,8.0,12.0,24.0,36.0,48.0,60.0,72.0 h of administration,and plasma was separated. RP-HPLC was used to determine the concentrations of RO and its metabolite arotinoid acetic acid(RA)in plasma. Using DAS 2.0 software for fitting,pharmacokinetic parameters were calculated. RESULTS:Both RO and RA showed a distribution in one-compartment model in dogs in vivo. The cmax of RO high-dose,medium-dose,low-dose groups in dogs in vivo were (0.42 ± 0.87),(0.54 ± 0.09),(0.31 ± 0.05)μg/mL;t1/2z were(1.20±0.33),(1.14±0.45),(1.90±0.65)h;AUC0-72 h were(3.55±0.90),(0.87±0.50),(0.92±0.31)μg·h/mL;and CL/F were(11.99±4.01),(19.87±10.79),(12.29±7.57)L/(kg·h). The cmax of RA high-dose,medium-dose,low-dose groups in dogs in vivo were (32.51 ± 4.04),(19.87 ± 2.78),(16.55 ± 4.06)μg/mL;t1/2z were (7.27 ± 4.20),(7.17 ± 4.20),(10.18 ± 4.01) h;AUC0-72 h were (408.14 ± 96.61),(333.39 ± 61.28),(286.55 ± 30.96)μg·h/mL;and CL/F were (1.30 ± 0.53)、(0.76 ± 0.87)、(0.54±0.10)L/(kg·h). CONCLUSIONS:Orally taking RO is easy to absorb with rapid elimination. Its active metabolite RA has longer accumulation time in vivo.