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.
ABSTRACT
We previously reported a large Chinese pedigree of erythrokeratodermia variabilis (EKV). A unique feature was that some of the affected members experienced transitory pustules on the border of classic lesions. Here we prescribed oral arotinoid ethylester and acitretin to two of the affected members in the pedigree, at starting dosage of 0.03 mg/day for arotinoid ethylester and 30 mg/day for acitretin, maintenance dosage of 0.03 mg every other day and 20 mg/day, respectively. Both patients reached complete clearance of the lesions during the treatment period. Side effect was negligible for the case on arotinoid ethylester. The patient on acitretin experienced elevated level of serum triglyceride and alanine aminotransferase that restrained further use.
