Pharmacokinetics and pharmacodynamics of cisatracurium in children undergoing cleft lip or cleft palate repair surgery

Wei-jia HAO,LI Jing-yi,2,Yi MA,Jie XIONG,Ping-xiang XU,Yu-hang LI,Xiao-tong ZHANG,Xiao-rong LI

(Capital Medical University,1.Department of Pharmacology,School of Basic Medical Sciences,2.Beijing Friendship Hospital,3.Beijing Stomatological Hospital,Beijing 100069,China)

T3-11

Pharmacokinetics and pharmacodynamics of cisatracurium in children undergoing cleft lip or cleft palate repair surgery

Wei-jia HAO1,LI Jing-yi1,2,Yi MA1,Jie XIONG1,Ping-xiang XU1,Yu-hang LI1,Xiao-tong ZHANG3,Xiao-rong LI1

(Capital Medical University,1.Department of Pharmacology,School of Basic Medical Sciences,2.Beijing Friendship Hospital,3.Beijing Stomatological Hospital,Beijing 100069,China)

OBJECTIVEThe aim of the study was to characterize the pharmacokinetics(PK)and pharmacodynamics(PD)profile of cisatracurium in 0-2 years and 2-5 years old children patients with cheilopalatognathus,to find if there are some connections between the different muscle relaxation action and different PK procedure.METHODS14 children patients were divided into two groups,≤2 years and 2-5 years group,venous samples were taken before injection of a 0.15 mg·kg-1dose of cisatracurium and then at 2,5,10,30,60,90,and 120 min.Cisatracurium plasma concentrations were determined by ultra-performance liquid chromatography/electrospray ionization/triple quadrupole tandem mass spectrometer system(UPLC/MS/MS).The degree of neuromuscular block was measured by train of four(TOF)testing.An indirect PK-PD link model with a sigmoid Emaxmodel was established using Win Nonlin software.The model were applied to PK and PD data analysis,respectively.RESULTSThe TOF monitor parameters showed that cisatracurium works very quickly,the onset time were(2.64±0.93)min and(2.59±0.90)min for≤2 years and 2-5 years group respectively.Young children ≤2 years have longer muscle blocking duration time(62.5±6.01 min vs 53.86±12.18 min)and slower recovery index(32.14±7.10 min and 27.43±10.63 min)than those children in group of 2-5 years.More children≤2 years have postoperative complication than that in 2-5 children.PK parameters showed that there were no statistical differences in blood concentration and pharmacokinetic parameters.While the concentration of cisatracurium in muscle site calculated by using PK/PD model were higher and longer for≤2 year children than that of 2-5 year children.This means that cisatracurium could stay at high concentration for a longer time in younger children′muscle tissue.CONCLUSIONAs a result young children tend to have postoperative complications related to slower muscle recovery action and increased concentration in skeletal muscle.So more careful observation and monitor are needed for younger children,our study could be of use in clinical practice for the administration of cisatracurium to children patients.

cisatracurium;children;PK/PD

The project supported by Top Young Innovative Talents of Beijing（CIT&TCD201404174）;and Basic Clinical Cooperation Project of Capital Medical University（14JL79）

Xiao-rong LI,E-mail:madingdaier@aliyun.com;Xiao-tong Zhang,E-mail:zxtbjkqyy@sohu.com