丙磺舒对家兔体内头孢克罗的药动学影响_论文.docxVIP

丙磺舒对家兔体内头孢克罗的药动学影响 【摘要】 目的 研究不同剂量丙磺舒(PBC)对头孢克罗(CCL)药动学的影响，探讨两药单次联用时最佳比例。方法 家兔42只，随机分成7组：Ⅰ组单用CCL 50mg/kg；Ⅱ～Ⅵ组CCL 50mg/kg分别联用PBC 50、100、200、300及400mg/kg；Ⅶ组CCL 25mg/kg联用PBC 100mg/kg。两药均灌胃给予。给药后不同时间点取血,HPLC法测定CCL血药浓度。结果 ①在实验剂量范围内，随着PBC剂量增大，CCL的t1/2ke、t1/2ka、tmax、MRT持续延长，PBC剂量较大时各值较CCL单用时有显著差异(P 【关键词】 丙磺舒 头孢克罗 药动学 HPLC 家兔 Effects of probenecid on the pharmacokinetics of cefaclor in rabbits ABSTRACT Objective To investigate effects of probenecid (PBC) at different doses on the pharmacokinetics of cefaclor (CCL) and to explore a suitable proportion of their single coadministration. Methods Fortytwo rabbits were randomly divided into 7 groups: CCL 50 mg/kg, alone CCL 50 mg/kg combined with PBC 50 mg/kg, CCL 50 mg/kg combined with PBC 100 mg/kg, CCL 50 mg/kg combined with PBC 200 mg/kg, CCL 50 mg/kg combined with PBC 300 mg/kg, CCL 50 mg/kg combined with PBC 400 mg/kg, CCL 25 mg/kg combined with PBC 100 mg/kg. Both drugs were given through intragastric administration, but CCL was 30 min later than PBC. Blood samples were drawn from thigh vein at 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 and 360 min after CCL administration. Plasma CCL concentration were determined by HPLC method, and the pharmacokinetic parameters were calculated with 3P87 programme. Results ① Concentrationtime course of CCL in plasma fitted a onecompartment open model. ② Within the range of experimental dosages, continuous prolongation in t1/2ke and MRT were observed, which showed a dosedependent relationship with the increase dosage of PBC the values of r were and , respectively; t1/2 and tmax prolong when higher doses of PBC ( ) were used and showed significant difference compared with I (CCL 50 mg/kg administration alone) (P KEY WORDS Probenecid; Cefaclor; Pharmacokinetics; HPLC; Rabbit 丙磺舒(probenecid，PBC)为一促尿酸排泄药，是许多药物经肾小管主动排泌的抑制剂［1］。自Beyer发现PBC可提高青霉素的血药水平之后，相继发现丙磺舒对多种β内酰胺类抗生素的药动学均有影响，如延缓后者的排泄，提高血药浓度，延长半衰期等。临床上PBC可作为某些β内酰胺类抗生素的辅助剂，以提高抗生素的血药浓度，延长其抗菌作用时间［2，3］。头孢克罗(cefaclor，