泊沙康唑注射液在侵袭性真菌病高危患者中的药代动力学和安全性评价

Pharmacokinetics and safety of posaconazole injection in subjects at high risk for invasive fungal disease

目的评价泊沙康唑注射液在治疗侵袭性真菌感染的高危受试者中的药代动力学(PK)特征和安全性。方法纳入中国10家医院血液血液病中心65例侵袭性真菌感染的高危受试者,分为A组20例,B组45例。A组受试者第1~10 d给予泊沙康唑注射液300 mg(第1 d,bid;第2~10 d,qd);第11~28 d能耐受口服的受试者转为泊沙康唑口服混悬液给药200 mg,tid。B组第1~5 d给予泊沙康唑注射液300 mg(第1 d,bid;第2~5 d,qd);第6~28 d,能耐受口服的受试者转为泊沙康唑口服混悬液200 mg,tid。观察PK指标、安全性指标及疗效指标。结果58例PK数据集(A组17例、B组41例)中,有57例的受试者静脉给药第3 d的C_(min)值在500~2500 ng·mL^(-1)之间;A组、B组转为口服混悬液后,口服混悬液的C_(min)值变异比静脉注射液的更大[CV:30.60%~49.95%(静脉);25.21%~87.42%(口服)];A组静脉给药后第10 d的T_(max)与原研产品研究结果类似,C_(max)、C_(min)、C_(avg)和AUC_(0-24 h)略高于原研产品研究结果。泊沙康唑的暴露与药物相关的不良事件发生率无明显关联,与原研结论基本一致。结论泊沙康唑注射液疗效肯定,安全可靠,PK参数与原研一致,可作为侵袭性真菌感染的高危患者的预防药物。

Objective To evaluate the pharmacokinetic(PK)characteristics and safety of Posaconazole injection in the treatment of high-risk subjects with invasive fungal disease.Methods 65 subjects with high risk of invasive fungal disease from multiple centers were enrolled and divided into group A(n=45)and group B(n=45).Group A received posaconazole injection 300 mg(day 1,bid;day 2-10,qd);subjects who could tolerate oral administration on day 11 to 28 were transferred to posaconazole oral suspension at 200 mg,tid.Group B was given posaconazole injection 300 mg(day 1,bid;day 2-5,qd);from day 6 to 28,subjects who could tolerate oral administration were switched to posaconazole oral suspension 200 mg,tid.Pharmacokinetic index,safety index and curative effect index were observed.Results In 58 pharmacokinetics(PK)data sets(17 cases in group A and 41 cases in group B),57 cases with C_(min) value between 500 ng·mL^(-1) and 2500 ng·mL^(-1) on day 3 of intravenous administration.The C_(min) variation of oral suspension in group A and B was greater than that of injection[CV:30.60%-49.95%(iv);25.21%~87.42%(po)];T_(max) of group A on day 10 after intravenous administration was close to the original study result,while C_(max),C_(min),Cavg and AUC_(0-24h) were all higher than the original study result.There was no significant relationship between posaconazole exposure and the incidence of drug-related adverse events,which was basically consistent with the conclusions of the original study.Conclusion Posaconazole injection has definite efficacy,is safe and reliable,and its PK parameters are consistent with the original study.It can be used as a prophylactic agent for patients at high risk of invasive fungal infection.