Optimal Teicoplanin Dosage Regimens in Critically Ill Patients: Population Pharmacokinetics and Dosing Simulations Based on Renal Function and Infection Type

Wang, Yifan1,2; Yao, Fen2; Chen, Shenglong3; Ouyang, Xin4; Lan, Jinhua5; Wu, Zheng2; Wang, Yirong2; Chen, Jingchun2; Wang, Xipei3,4,6,7; Chen, Chunbo1

2023

10.2147/DDDT.S413662

DRUG DESIGN DEVELOPMENT AND THERAPY   Impact Factor & Quartile

1177-8881

Purpose: To develop a population pharmacokinetic model describing teicoplanin concentrations in patients hospitalized in intensive care unit (ICU) and to perform Monte Carlo simulations to provide detailed dosing regimens of teicoplanin. Methods: This single-center, prospective, observational study was conducted on 151 patients in ICU with 347 plasma samples. The population pharmacokinetics model was established and various covariates were evaluated. The probability of target attainment (PTA) of various proposal dosing regimens was calculated by Monte Carlo simulations. Results: The two-compartment model adequately described teicoplanin concentration-time data. The estimated glomerular filtration rate (eGFR) associated with systemic clearance (CL) was the only covariate included in the final model. The estimate of CL was 0.838 L/h, with the eGFR adjustment factor of 0.00823. The volume of the central compartment (Vc), inter-compartmental clearance (Q) and volumes of the peripheral compartments (Vp) were 14.4 L, 3.08 L/h and 51.6 L, respectively. The simulations revealed that the standard dosage regimen was only sufficient for the patients with severe renal dysfunction (eGFR & LE; 30 mL/min/ 1.73 m2) to attain target trough concentration (Cmin, PTA 52.8%). When eGFR > 30 mL/min/1.73 m2, increasing dose and the administration times of loading doses were the preferred options to achieve target Cmin based on the renal function and types of infection. Conclusion: The most commonly used standard dosage regimen was insufficient for all ICU patients. Our study provided detailed dosing regimens of teicoplanin stratified by eGFR and types of infection for ICU patients.

teicoplanin pharmacokinetics Monte Carlo simulation intensive care unit renal function

SCI

English

First ; Corresponding

Guangzhou Science and Technology Program[201803010058] ; National Natural Science Foundation of China["82070254","82170415","82172162"] ; Major Program of Summit Project, Guangdong Province High-level Hospital Construction Project of Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences[DFJH2020028] ; Science and Technology Program of Guangzhou[202102080011] ; Natural Science Foundation of Guangdong[2021A1515011554]

Pharmacology & Pharmacy

Chemistry, Medicinal ; Pharmacology & Pharmacy

WOS:001044786800001

DOVE MEDICAL PRESS LTD

Web of Science

1.Southern Univ Sci & Technol, Second Clin Med Coll Jinan Univ, Shenzhen Peoples Hosp, Affiliated Hosp 1,Dept Crit Care Med, Shenzhen 518020, Peoples R China
2.South China Univ Technol, Sch Biol & Biol Engn, Guangzhou 510006, Peoples R China
3.Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Dept Crit Care Med, Guangzhou 510080, Peoples R China
4.Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Guangdong Cardiovasc Inst, Dept Intens Care Unit Cardiovasc Surg, Guangzhou 510080, Peoples R China
5.Gen Hosp Southern Theatre Command, Dept Pharm, Guangzhou 510010, Peoples R China
6.Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Res Ctr Med Sci, Guangzhou 510080, Peoples R China
7.Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Guangdong Cardiovasc Inst, Guangdong Prov Key Lab Clin Pharmacol, Guangzhou 510080, Peoples R China

Wang, Yifan,Yao, Fen,Chen, Shenglong,et al. Optimal Teicoplanin Dosage Regimens in Critically Ill Patients: Population Pharmacokinetics and Dosing Simulations Based on Renal Function and Infection Type[J]. DRUG DESIGN DEVELOPMENT AND THERAPY,2023,17.

Wang, Yifan.,Yao, Fen.,Chen, Shenglong.,Ouyang, Xin.,Lan, Jinhua.,...&Chen, Chunbo.(2023).Optimal Teicoplanin Dosage Regimens in Critically Ill Patients: Population Pharmacokinetics and Dosing Simulations Based on Renal Function and Infection Type.DRUG DESIGN DEVELOPMENT AND THERAPY,17.

Wang, Yifan,et al."Optimal Teicoplanin Dosage Regimens in Critically Ill Patients: Population Pharmacokinetics and Dosing Simulations Based on Renal Function and Infection Type".DRUG DESIGN DEVELOPMENT AND THERAPY 17(2023).