氯替泼诺不同给药途径在比格犬体内药物动力学

Pharmacokinetics of loteprednol etabonate in beagle dogs through different routes of administration

目的考察不同给药途径比格犬体内氯替泼诺的药动学行为,为临床用药安全提供参考。方法比格犬分别滴眼给予氯替泼诺滴眼剂(受试制剂)或口服给予氯替泼诺胶囊(参比制剂),采用高效液相色谱法测定血浆中氯替泼诺的非活性代谢物PJ90和PJ91的药物浓度。结果滴眼给药后血浆中未检到氯替泼诺代谢物PJ90和PJ91。口服给药后血浆中氯替泼诺代谢物PJ90和PJ91的主要药动学参数分别为:T_(max)(1.38±0.89)h和(1.17±0.90)h,ρ_(max)分别为(0.35±0.05)mg/L和(0.24±0.13)mg/L,t_(1/2)分别为(7.11±3.76)h和(14.95±9.30)h,用梯形法计算,AUC_(0-t)分别为(2.12±1.42)mg/(h·L)和(2.02±1.29)mg/(h·L),AUC_(0-∞)分别为(2.81±1.83)mg/(h·L)和(3.97±3.23)mg/(h·L)。结论氯替泼诺滴眼给药后是安全的。

Objective To investigate the pharmacokinetics of loteprednol etabonate in beagle dogs through different routes of administration,and to provide reference for clinical medication safety.Methods Beagle dogs were given loteprednol etabonate eye drops（test preparation）or oral administration of loteprednol etabonate capsules（reference preparation）.Concentration of PJ90 and PJ91,which were non active metabolite of loteprednol etabonate,was determined by HPLC method.Results PJ90 and PJ91 were not detected after administration of eye drops.After oral administration,the main pharmcokinetic parameters of PJ90 and PJ91 in the plasma were as follows：Tmax was（1.38±0.89）h and（1.17±0.90）h,ρmax was（0.35±0.05）mg/L and（0.24±0.13）mg/L,t1/2 was（7.11±3.76）h and（14.95±9.30）h,AUC0-t was（2.12±1.42）mg/（h·L）and（2.02±1.29）mg/（h·L）,and AUC0-∞was（2.81±1.83）mg/（h·L）and（3.97±3.23）mg/（h·L）.Conclusion Loteprednol etabonate eye drops are safe.