同时利用血药数据和尿药数据研究头孢拉定在家兔体内的药代动力学及其肾排泄

Pharmacokinetics of cephradine in rabbits and its renal excretion by use of both plasma and urinary data

关键词:  头孢拉定  药动学  高效液相色谱  肾排泄  家兔

Key words:  cephradine  pharmacokinetics  HPLC  renal excretion  rabbit

摘要:

［目的］研究头孢拉定（cephradine，CED）在家兔体内的药代动力学行为和肾排泄机制，为CED的临床用药提供动物实验依据。［方法］采用反相HPLC法测定家兔血浆和尿液样品中CED浓度。家兔iv注射CED高（100 mg/kg）、中（50 mg/kg）、低（25 mg/kg）剂量后不同时间分别收集血样和尿液，三氯醋酸沉淀蛋白后进样分析，以峰面积内标法定量。血肌酐和尿肌酐浓度应用苦味酸法测定。分别以血药浓度数据和尿排泄数据求算CED药动学参数，通过清除率CL的测定和比较探讨CED的肾排泄机制。［结果］方法学验证表明本文采用的HPLC法特异性、精密度和回收率符合药动学研究要求。CED iv的血药浓度时程符合二室模型、线性动力学。其t_1/2β为88.01~ 91.83 min，MRT为57.49~83.84 min，说明消除快速。尿药数据用亏量法解析，其log（X_u∞-X_ut）-t作图符合静注二室模型，求得CED的t_1/2β为76.93~79.56 min，MRT为61.41~74.01 min，与血药数据差异无显著性意义。CED的CL_t和CL_R分别为10.22~12.89 mL·min^-1·kg^-1和5.20~6.66 mL·min^-1·kg^-1，CLCR 为2.95~3.30 mL·min^-1·kg^-1。［结论］CED在家兔的药动学行为采用血药数据和尿药数据同时研究所得结果一致，均呈线性动力学，且消除快速。并提示除通过肾清除外,还存在明显的肾外清除机制；CED经肾排泄过程中既包括肾小球滤过又存有肾小管的主动分泌。

Abstract:

［Objective］To study pharmacokinetics (PK) of cephradine (CED) in rabbits and its renal exerction by means of both plasma and urinary data, and thereby provide experimental data for the clinical application of CED.［Methods］After deproteinized with 10% TCA,Plasma and urine samples were assayed by RP-HPLC method. Creatinine concentration in plasma and urine was measured with reference to Jaffe's picrate method and used to calculated CL_CR . The PK parameters were obtained by use of plasma drug data and urinary drug data, respectively. The renal handle of CED was studied by comparing CL,CL_R and CL_CR .［Results］The HPLC method showed high specificity, precision and recovery, and complied with requirements of PK research . The PK behaviour of CED in plasma complied with two-compartment model and first order kinetics.The t_1/2β 88.01~ 91.83 min and MRT 57.49~83.84 min indicate a rapid elimination of CED. Sigma-minus method was used for urinary PK analysis. The log（X_u∞-X_ut）-t curve could be described by the two-compartment model with t_1/2β 76.93~79.56 min, MRT61.41~74.01 min, CL_t 10.22~12.89 mL min^-1 kg^-1 , CLR 5.20~6.66 mL min^-1 kg^-1 , CLCR 2.95~3.30 mL min^-1 kg^-1 .［Conclusions］The PK behavior of CED investigated using urinary excretion data are in good agreement with those using plasma data, and all indicate a rapid elimination of CED. CED follows linear PK in the studied dose range, and eliminates not only by renal route but also by non-renal route. It is reasoned that CED excretes into urine by both renal glomerular filtration and active tubular secretion.