Brown S A, Boucher J F, Hubbard V L, Prough M J, Flook T F
Veterinary Medicine Research & Development, Pfizer Animal Health, Kalamazoo, MI 49001, USA.
J Vet Pharmacol Ther. 2007 Aug;30(4):320-6. doi: 10.1111/j.1365-2885.2007.00873.x.
The pharmacokinetic properties of cefpodoxime, and its prodrug, cefpodoxime proxetil, were evaluated in two separate studies, one following intravenous (i.v.) administration of cefpodoxime sodium and the second after oral (p.o.) administration of cefpodoxime proxetil to healthy dogs. After cefpodoxime administration, serial blood samples were collected and plasma concentrations were determined by high performance liquid chromatography (HPLC). A single i.v. administration of cefpodoxime sodium at a dose of 10 mg cefpodoxime/kg body weight resulted in a cefpodoxime average maximum plasma concentration (Cmax) of 91 (+/-17.7) microg/mL, measured at 0.5 h after drug administration, an average half-life (t1/2) of 4.67 (+/-0.680) h, an average AUC(0-infinity) of 454 (+/-83.1) h.microg/mL, an average V(d(ss)) of 151 (+/-27) mL/kg, an average Cl(B) of 22.7 (+/-4.2) mL/h/kg and an average MRT(0-infinity) of 5.97 (+/-0.573) h. When dose normalized to 10 mg cefpodoxime/kg body weight, cefpodoxime proxetil administered orally resulted in Cmax of 17.8 +/- 11.4 microg/mL for the tablet formulation and 20.1 +/- 6.20 microg/mL for the suspension formulation and an average AUC(0-LOQ) of 156 (+/-76.1) h.microg/mL for the tablet formulation and 162 (+/-48.6) h.microg/mL for the suspension formulation. Relative bioavailability of the two oral formulations was 1.04 (suspension compared with tablet), whereas the absolute bioavailability of both oral formulations was estimated to be approximately 35-36% in the cross-study comparison with the i.v. pharmacokinetics. Combined with previous studies, these results suggest that a single daily oral dose of 5-10 mg cefpodoxime/kg body weight as cefpodoxime proxetil maintains plasma concentrations effective for treatment of specified skin infections in dogs.
在两项独立研究中评估了头孢泊肟及其前药头孢泊肟酯的药代动力学特性，一项研究是对健康犬静脉注射头孢泊肟钠，另一项是对健康犬口服头孢泊肟酯。给予头孢泊肟后，采集系列血样，采用高效液相色谱法（HPLC）测定血浆浓度。以10mg头孢泊肟/ kg体重的剂量单次静脉注射头孢泊肟钠后，给药后0.5小时测得头孢泊肟平均最大血浆浓度（Cmax）为91（±17.7）μg/mL，平均半衰期（t1/2）为4.67（±0.680）小时，平均AUC(0-∞)为454（±83.1）h·μg/mL，平均稳态分布容积（V(d(ss))）为151（±27）mL/kg，平均清除率（Cl(B)）为22.7（±4.2）mL/h/kg，平均药时曲线下面积（MRT(0-∞)）为5.97（±0.573）小时。当剂量归一化为10mg头孢泊肟/ kg体重时，口服头孢泊肟酯，片剂制剂的Cmax为17.8±11.4μg/mL，混悬液制剂的Cmax为20.1±6.20μg/mL；片剂制剂的平均AUC(0-LOQ)为156（±76.1）h·μg/mL，混悬液制剂的平均AUC(0-LOQ)为162（±48.6）h·μg/mL。两种口服制剂的相对生物利用度为1.04（混悬液相对于片剂），而在与静脉注射药代动力学的交叉研究比较中，两种口服制剂的绝对生物利用度估计约为35%-36%。结合先前的研究，这些结果表明，以头孢泊肟酯形式每日口服5-10mg头孢泊肟/ kg体重可维持有效治疗犬特定皮肤感染的血浆浓度。
