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目的利用临床手术治疗下给药后血和组织标本动态采集模型,对头孢哌酮(CPZ)在血液和胰腺组织中穿透的药动学及药效学进行评价。方法手术采集26名接受2 g舒普深输注病人在0～12 h随机分布的血浆和胰腺组织标本;采用HPLC测定获得CPZ药-时数据和曲线;用WinNonlin软件的非房室模型计算出血和胰腺组织PK参数,以及药-时曲线大于MIC作用时间占给药间隔的百分比(%T>MIC)、给药后动态穿透率PR0-12 h及穿透指数PI,对CPZ在胰腺组织中的杀菌作用进行药效学评价。结果 CPZ给予1g/Q12恒速45 min输注后其胰腺组织药物浓度较高且达峰晚于血药峰值,其血和胰腺组织tmax分别为0.75和4.0 h,ρmax分别为83.50 mg·L-1和23.25 mg.kg-1,AUC0-12分别为298.82 mg.h.L-1和98.08 mg.h.kg-1,平均PR0-12 h可达(41.55±21.38)%,PI为32.82%;血和胰腺组织药-时曲线符合一室模型特征,二者消除基本平行,t1/2分别为2.21和2.82 h。CPZ血和组织药物浓度的%T>MIC分别为:MIC=8时,为81.3%和50.0%;MIC=16时,为62.5%和33.3%。结论该组织标本动态采集模型可不干扰临床治疗下进行药物剂量方案的PK和PD研究;CPZ在胰腺中穿透率较高且组织消除与血药基本平行;1g/Q12恒速45 min输注CPZ可满足一般胰腺感染治疗,严重感染时Q8给药可达理想杀菌效果。
OBJECTIVE: To evaluate the pharmacokinetics and pharmacodynamics of cefoperazone (CPZ) penetrating blood and pancreatic tissue by using dynamic collection of blood and tissue samples after clinical administration. Methods Twenty-six plasma and pancreatic tissue samples were randomly collected from 0 to 12 h in patients receiving infusion of 2 g Shuxu Shen, and CPZ drug-time data and curves were obtained by HPLC. The non-compartmental model of WinNonlin software was used to calculate Bleeding and pancreatic tissue PK parameters, and drug-time curve is greater than the percentage of the role of MIC time interval (% T> MIC), after administration of dynamic penetration PR0-12 h and penetration index PI, CPZ in the pancreas The bactericidal effect in the tissue was evaluated pharmacodynamically. Results CPZ given a constant 45-minute infusion of 1g / Q12 pancreatic tissue drug concentration was higher and reached a peak later than the plasma peak value, the blood and pancreatic tissue tmax were 0.75 and 4.0 h, ρmax were 83.50 mg · L- 1 and 23.25 mg.kg-1, respectively. The AUC0-12 values were 298.82 mg.hL-1 and 98.08 mg.h.kg-1 respectively, with a mean of 41.55 ± 21.38% and a PI of 32.82% And pancreatic tissue drug-time curve were consistent with the characteristics of one-compartment model, the two were basically parallel to eliminate, t1 / 2 were 2.21 and 2.82 h. The% T> MIC of CPZ blood and tissue drug concentration were 81.3% and 50.0% for MIC = 8, 62.5% and 33.3% for MIC = 16, respectively. Conclusions The model of dynamic acquisition of tissue samples can not interfere with the PK and PD studies of drug dosage regimen under clinical treatment. CPZ has higher penetration rate in pancreatic tissue and the tissue elimination is basically parallel with blood drug; 1 g / Q12 infusion of CPZ Can meet the general treatment of pancreas infection, Q8 administration of severe infections up to the desired bactericidal effect.