Population pharmacokinetics of anti-viral drugs in COVID-19 patients: A clinical perspective
Suong NT Ngo. School of Animal & Veterinary Sciences, The University of Adelaide1, Adelaide, SA, Australia.
Objective. The aim of this study is to systematically review and summarise human clinical studies that aimed to develop and applied population pharmacokinetic model(s) for anti-viral drug therapy in COVID-19 patients.
Methods. A systematic review was conducted in PubMed, EMBASE, and the Cochrane Library from January 2020 to 11 January 2022. Peer-reviewed clinical studies, published in English which investigated pharmacokinetics of antiviral drug therapy in COVID-19 patients were selected. The key search terms used were “population pharmacokinetics” AND “antiviral drugs” AND “COVID-19”. Key inclusion criteria include 1) studies applied population pharmacokinetics, 2) studies investigated antiviral drug therapy, and 3) studies examined COVID-19 patients.
Results and Discussion. The systematic literature search identified 4 clinical studies which met the selection criteria. These studies examined and applied population pharmacokinetic model(s) for optimising antiviral drug therapy in COVID-19 patients. The investigated drugs were lopinavir/ritonavir, darunavir, favipiravir and bamlanivimab and etesevimab antibodies. Of the included studies, three out of four studies involved a relatively small number of COVID-19 patients, approximately 10 to 40 patients (as shown in Table 1 below).
Studies utilised in silico approaches, stimulation for dosage and PKs prediction and/or investigated other repurposing drugs rather than antiviral drugs were excluded. Three RCTs not met selection criteria were also excluded. Key findings from this study will be further discussed at the PAGANZ virtual meeting.
Table 1. Summary of clinical studies investigated population pharmacokinetics of antiviral drug therapy in COVID-19 patients
|
Study ID |
Patients |
Drugs |
Covariates |
Program/Software |
|
Alvarez et al 20201
|
13 hospitalized patients 4F; 9M > 65 year |
Lopinavir/ritonavir
|
Age, weight, BMI, gender, creatinine, AST, ALT, and rough ritonavir conc
|
NONMEM version 7.4
|
|
Chigutsa et al 20212
|
2970 patients with early mild to moderate disease |
Bamlanivimab and etesevimab
|
Age, sex, race, baseline viral load, and hepatic impairment
|
NONMEM version 7.4.2 |
|
Cojutti et al 20203
|
30 admitted patients |
Darunavir
|
Age, sex, BSA, height, weight, albumin, ALT, ALT, creatinine, bilirubin, AST, γ-GT, IL-6, and disease stage
|
Monolix version 2019R1
|
|
Irie et al 20214 |
39 patients 8F; 31M 27 – 89 year |
Favipiravir
|
Age, sex, BW, HT, BSA, BMI, AST, ALT, SCr, comedications, and disease stage
|
NONMEM version 7.41
|
1Alvarez et al., 2021. Eur J Clin Pharmacol. 77(3): 389-97.
2Chigutsa et al., 2021. J. Clin Pharmacol Ther. 110(5): 1302-10.
3Cojutti et al., 2020. Clin Pharmacokinet. 59(10): 1251-1260.
4Irie et al., 2021. CPT Pharmacometrics Syst Pharmacol. 10(10): 1161-70.