Peptide Carrier-Mediated Transport in Intestinal Brush Border Membrane Vesicles of Rats and Rabbits: Cephradine Uptake and Inhibition

The uptake kinetics of cephradine, an amino--lactam antibiotic, were studied in rat and rabbit intestinal brush border membrane vesicles preparations using both the Ca²⁺ and the Mg²⁺ methods of preparation, in the presence of an inward proton gradient. The Ca²⁺ method demonstrated greater uptake of cephradine in intestinal brush border vesicles prepared from both rat and rabbit and was used for these studies. The transport was observed to be of Michaelis–Menten carrier-mediated type with a passive transport component. The kinetic parameters obtained were as follows: for rat and rabbit, respectively, K _m, 1.6 and 1.9 mM; J _max, 1.7 and 20.7 nmol/mg/min; P _c (= J _max/K _m), 1.1 and 10.9 µL/mg/min; and P _m, 0.4 and 0.8 µL/mg/min. The kinetic parameters for the rat vesicles are consistent with those from our previous perfusion study using a conversion factor of 0.71 cm²/mg protein. The rabbit vesicles exhibited a similar Michaelis constant and a 10-fold larger maximal transport velocity, suggesting a quantitative advantage for the study of carrier-mediated transport in the rabbit compared to rat vesicles from the intestine. Cephradine uptake was inhibited by phenylpropionylproline, a proline derivative, and enalapril, an ACE inhibitor, which do not have an -amino group, as well as dipeptides, tripeptides, and amino--lactam antibiotics in both rat and rabbit vesicles. These results support the suggestion that they share the same peptide carrier pathway for oral absorption and that the vesicles may be a useful tool in developing orally effective peptide-type drugs.     

头孢拉定对奈替米星药代动力学的影响

目的 观察头孢拉定对奈替米星药代动力学的影响。方法１４例感染患者随机分成单用奈替米星组（ＮＴＭ）和奈替米星＋头孢拉定组（ＮＴＭ＋ＣＰＲ）。采用高效液相色谱一间接光度检测（ＨＰＬＣ－ＩＰＤ）法，测定患者单剂量静脉滴注 ５ ｍｇ ＮＴＭ后的血清药物浓度，并计算主要药动学参数；同时测定尿液药物浓度及药物回收率。结果ＮＴＭ组和ＮＴＭ＋ＣＰＲ组的Ｔ１／１／２β分别为２．４０±１．０１ｈ和 ４．３３± １．４３ｈ（Ｐ＜ ０．０１），ＡＵＣ０～２４ｈ６３．４２± ３０．００ｍｇ／Ｌ·ｈ和 ７８．５４± ３２．８８ｍｇ／Ｌ·ｈ（ｐ＜ ０．０ １），２４ｈ尿中 ＮＴＭ Ｗ收率也有显著性差异。结论 ＮＴＭ＋ＣＰＲ联用时 ＮＴＭ生物利用度增高，尿中回收率下降，连续长期联用将导致体内蓄积。     

盐酸山莨菪碱对头孢拉定注射液稳定性的影响

目的:研究盐酸山莨菪碱(654-2)对头孢拉定(Cep)注射液稳定性的影响.方法:采用反相高效液相色谱法测定3种温度F,不同时间的Cep在生理盐水和含654-2盐水中的含量.结果:两组数据经统计学处理无显著性差异.结论:Cep与654-2配伍时其含量稳定.     

固定化青霉素酰化酶合成头孢拉定的工艺研究

用7-氨基-3-脱乙酰氧基头孢霉烷酸和2,5-二氢苯甘氨酸甲酯盐酸盐在磷酸盐缓冲液体系中（20℃,pH 7.0）,利用固定化青霉素酰化酶催化合成抗生素头孢拉定,收率90%。