Pharmacokinetics,pharmacodynamics of esomeprazole in critically ill patients
10.12092/j.issn.1009-2501.2024.10.008
- VernacularTitle:艾司奥美拉唑在重症患者体内药代/药效学研究
- Author:
Xian ZHA
1
;
Luning SUN
;
Chao CHEN
;
Yongqing WANG
Author Information
1. 南京医科大学第一附属医院药学部,南京 210029,江苏;东南大学附属中大医院药学部,南京 210009,江苏;江苏省重症医学重点实验室,东南大学附属中大医院重症医学科,南京 210009,江苏
- Keywords:
esomeprazole;
pharmacokinetics;
pharmacodynamics;
critical illness
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2024;29(10):1152-1160
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the pharmacoki-netic/pharmacodynamic(PK/PD)profile of esome-prazole for injection in critically ill patients.METH-ODS:This was a prospective,single-center,open-la-bel study,all patients received intravenous infused esomeprazole 40 mg q12h for stress ulcer prophy-laxis,treatment duration is determined by clini-cians based on patients condition.Forty critically ill patients were enrolled and were divided into single and multiple dose groups according to the timing of blood sample collection.Twenty-one patients in the single-dose group had their blood samples col-lected at 1,3,6,8,and 12 h after the first dose,and 34 patients in the multiple-dose group had their blood samples collected at 0 h before the fifth dose and 1,3,6,and 8,and 12 h after the fifth dose,of which 14 patients had their blood samples collected at both the first dose and the repeated doses.The concentration of esomeprazole was measured by HPLC-MS/MS,and PK parameters were analyzed using noncompartmental analysis.Gastric aspirates were collected for pH measure-ment in fasted patients with gastric tube before the first dose(0 h),and 1,2,4,8,12,14,16,20,24 h after the initiation of drug administration,and the percentage of time with pH≥4 was calculated.All adverse events and serious adverse events during treatment were recorded.RESULTS:Patients in the single-dose group were 67.75 years old(45-69 years)with a BMI(24.05±3.35)kg/m2,and pa-tients in the multiple-dose group were 63.35 years old(24-87 years)with a BMI(24.08±3.29)kg/m2.PK parameters after the first dose were AUC0-t(11.26±6.58)mg·h·L-1,Cmax(3.08±2.06)mg/L,CL(4.13±3.68)L/h,Vd(17.12±6.13)L,t1/2(4.80±3.06)h;PK parameters after multiple doses were AUC0-t(16.70±11.20)mg·h/L,Cmax(3.37±2.59)mg/L,CL(3.94±2.94)L/h,Vd(22.71±17.26)L,t1/2(5.23±3.34)h.Percentage of time with pH≥4 with-in 0 h-24 h after administration was 61.69％,and percentage of time with pH≥4 within 12 h-24 h was up to 100％.Esomeprazole was well tolerated by all patients with no serious adverse events.CONCLU-SION:Compared with healthy volunteers,inject-able esomeprazole showed increased Vd,decreased CL,increased drug exposure and accumulation af-ter repeated administration in critically ill patients.The drug had a favorable safety profile in critically ill patients.
