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PR_{0-12 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，AUC_0-12分别为298.82 mg·h·L-1和98.08 mg·h·kg-1，平均PR_{0-12 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 study the PK/PD of cefoperazone (CPZ in pancreatic tissue of patients using population pharmacokinetic sampling model. METHODS Blood and tissue samples were obtained simultaneously in pancreatectomy during 0-12 h after 45 min infusion administration of 2 g SUPERAZON (1 g CPZ， 1 g Sul in 26 patients. CPZ concentrations in plasma and tissue were determined by HPLC. The PK behavior and parameters were analyzed using WinNonlin(v5.2 program. The dynamic penetration ratios (PR_{0-12 h}， C_tissue/C_plasma， penetration index (PI， AUC_tissue/AUC_plasma， and %T>MIC were calculated， respectively. RESULTS The PK process of CPZ in plasma and tissue complied with one-compartment model. The tmax， ρmax， AUC_0-12 and t1/2 of CPZ in plasma and tissue were 0.75 and 4.0 h， 83.50 mg·L-1 and 23.25 mg·kg-1， 298.82 mg·h·L-1 and 98.08 mg·h·kg-1， 2.21 and 2.82 h， respectively. The average PR_{0-12 h} and PI were （41.55±21.38% and 32.82%， and the %T>MIC of CPZ in plasma and tissue were 81.3% and 50.0% when MIC=8， 62.5% and 33.3% when MIC=16， respectively. CONCLUSION The elimination phase of CPZ in plasma was similar to that in pancreatic tissue. After 45 min infusion administration of 2 g SUPERAZON， effective concentrations were obtained and maintained for 12 h in pancreatic tissue and plasma， and bactericidal efficacy was achieved for the treatment of pancreatitis and also for the prophylaxis of wound infection after pancreatectomy.