Population pharmacokinetics of nirmatrelvir/ritonavir in critically ill Chinese COVID-19 patients and recommendations for medication use: a two-center retrospective study

被引:0
作者
Xu, Junjun [1 ]
Li, Jinmeng [2 ]
Chen, Meng [1 ]
Jiang, Huifang [1 ]
Fan, Xudong [2 ]
Hu, Yangmin [1 ]
Shan, Haili [1 ]
Yang, Mingdong [1 ]
Xu, Yichao [1 ]
Lang, Yuying [2 ]
Dai, Haibin [1 ]
Cai, Xinjun [2 ]
机构
[1] Zhejiang Univ, Affiliated Hosp 2, Dept Pharm, Sch Med, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China
[2] Hangzhou Red Cross Hosp, Zhejiang Hosp Integrated Tradit Chinese & Western, Dept Pharm, Hangzhou 310000, Zhejiang, Peoples R China
关键词
Nirmatrelvir; ritonavir; population pharmacokinetics; critically ill patients; renal function;
D O I
10.1080/17512433.2024.2410385
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: This study aimed to establish population pharmacokinetics (PPK) models of nirmatrelvir/ritonavir in critically ill Chinese patients with the coronavirus disease 2019 (COVID-19) infection, explore factors affecting the pharmacokinetics (PK) of nirmatrelvir/ritonavir. Methods: A total of 285 serum samples and clinical data were collected from 152 patients. The PPK models of nirmatrelvir/ritonavir were analyzed using nonlinear mixed-effect modeling (NONMEM) approach. The optimal dosing regimen for patients with different renal function was determined using Monte Carlo simulations. Results: The population typical values of apparent clearance (CL/F) and apparent volume of distribution (V/F) of nirmatrelvir were 2.26 L/h and 15.3 L, respectively. Notably, creatinine clearance (CrCL) significantly influenced the PK variation of nirmatrelvir. Monte Carlo simulations suggested that patients with mild-to-moderate renal impairment experienced a 22.0-59.9% increase in the area under the curve (AUC) when they were administered a standard dose of nirmatrelvir compared to those with normal renal function. The AUC in patients with severe renal impairment after administration of 150 mg q12h nirmatrelvir was similar to that in patients with normal renal function after administration of 300 mg q12h nirmatrelvir. Conclusions: PPK modeling and simulation provided a reference for the rational clinical application of nirmatrelvir/ritonavir in critically ill Chinese patients.
引用
收藏
页码:1071 / 1079
页数:9
相关论文
共 34 条
  • [1] Efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) for COVID-19: A rapid review and meta-analysis
    Amani, Behnam
    Amani, Bahman
    [J]. JOURNAL OF MEDICAL VIROLOGY, 2023, 95 (02)
  • [2] Review of COVID-19 Therapeutics by Mechanism: From Discovery to Approval
    Choi, Hee Sun
    Choi, A. Young
    Kopp, Jeffrey B.
    Winkler, Cheryl A.
    Cho, Sung Kweon
    [J]. JOURNAL OF KOREAN MEDICAL SCIENCE, 2024, 39 (14)
  • [3] Adverse events related to drug-drug interactions in COVID-19 patients. A persistent concern in the post-pandemic era: a systematic review
    Conti, Valeria
    Bertini, Nicola
    Ricciardi, Rosaria
    Stefanelli, Berenice
    De Bellis, Emanuela
    Sellitto, Carmine
    Cascella, Marco
    Sabbatino, Francesco
    Corbi, Graziamaria
    Pagliano, Pasquale
    Filippelli, Amelia
    [J]. EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2024, 20 (04) : 275 - 292
  • [4] Identification of Drug Interaction Adverse Events in Patients With COVID-19 A Systematic Review
    Conti, Valeria
    Sellitto, Carmine
    Torsiello, Martina
    Manzo, Valentina
    De Bellis, Emanuela
    Stefanelli, Berenice
    Bertini, Nicola
    Costantino, Maria
    Maci, Chiara
    Raschi, Emanuel
    Sabbatino, Francesco
    Corbi, Graziamaria
    Pagliano, Pasquale
    Filippelli, Amelia
    [J]. JAMA NETWORK OPEN, 2022, 5 (04) : E227970
  • [5] Population Pharmacokinetics of Vancomycin in Patients Receiving Hemodialysis in a Malian and a French Center and Simulation of the Optimal Loading Dose
    Coulibaly, Balla
    Maire, Pascal
    Guitton, Jerome
    Pelletier, Solenne
    Tangara, Moustapha
    Aulagner, Gilles
    Goutelle, Sylvain
    [J]. THERAPEUTIC DRUG MONITORING, 2023, 45 (05) : 637 - 643
  • [6] Effects of nirmatrelvir/ritonavir on midazolam and dabigatran pharmacokinetics in healthy participants
    Cox, Donna S.
    Rehman, Muhammad
    Khan, Tahira
    Ginman, Katherine
    Salageanu, Joanne
    LaBadie, Robert R.
    Wan, Katty
    Damle, Bharat
    [J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2023, 89 (11) : 3352 - 3363
  • [7] Effects of itraconazole and carbamazepine on the pharmacokinetics of nirmatrelvir/ritonavir in healthy adults
    Cox, Donna S. S.
    Van Eyck, Lien
    Pawlak, Sylvester
    Beckerman, Bruce
    Linn, Carlos
    Ginman, Katherine
    Thay Cha, Youliny
    LaBadie, Robert R. R.
    Shi, Haihong
    Damle, Bharat
    [J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2023, 89 (09) : 2867 - 2876
  • [8] drugs, NIRMATRELVIR RITONAV
  • [9] Novel Investigational Anti-SARS-CoV-2 Agent Ensitrelvir "S-217622": A Very Promising Potential Universal Broad-Spectrum Antiviral at the Therapeutic Frontline of Coronavirus Species
    Eltayb, Wafa A.
    Abdalla, Mohnad
    Rabie, Amgad M.
    [J]. ACS OMEGA, 2023, : 5234 - 5246
  • [10] A Comprehensive Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Drug Interactions of Nirmatrelvir/Ritonavir
    Gerhart, Jacqueline
    Cox, Donna S.
    Singh, Ravi Shankar P.
    Chan, Phylinda L. S.
    Rao, Rohit
    Allen, Richard
    Shi, Haihong
    Masters, Joanna C.
    Damle, Bharat
    [J]. CLINICAL PHARMACOKINETICS, 2024, 63 (01) : 27 - 42