
Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.
Fixed Dosing of Tocilizumab in ICU Admitted COVID-19 Patients Is a Superior Choice Compared to Bodyweight Based Dosing; An Observational Population Pharmacokinetic and Pharmacodynamic Study
20 Pages Posted: 8 May 2021
More...Abstract
Background: Tocilizumab improves outcome, including survival, in intensive care unit (ICU) admitted COVID-19 patients. The currently applied dosage of 8 mg/kg is based on use of this drug for other indications, however is has not formally been investigated for COVID-19. In this study pharmacokinetics and dynamics of tocilizumab were investigated in ICU admitted COVID-19 patients.
Methods: This was an open-label, single-center observational pharmacokinetic and -dynamic evaluation study. Enrolled patients, with polymerase chain reaction confirmed Covid-19 were admitted to the ICU for mechanical ventilation or high flow nasal canula oxygen support. All patients were 18 years of age or older and received tocilizumab within 24 hours after admission to the ICU and received 6 mg dexamethasone daily as concomitant therapy.
Findings: 29 patients were enrolled between 15 December 2020 and 15 March 2021. A total of 139 tocilizumab plasma samples were obtained covering the pharmacokinetic curve of day 0 up to day 20 after tocilizumab initiation. A population pharmacokinetic model with parallel linear and non-linear clearance was developed and validated. Average AUC0-inf 1st DOSE was 938 [±190] ug/mL*days. Tocilizumab half-life was estimated to be 4·15 [±0·24] days. All patients had tocilizumab exposure above 1 ug/ml for at least 15 days.
Interpretation: This study provides evidence to support a fixed dose of 600 mg tocilizumab in COVID-19 patients. Furthermore our findings suggest that alternative cost saving regimens with even lower doses are likely to be as effective as the current 8 mg/kg recommendation.
Funding: No external funding was received for this work.
Declaration of Interests: N.A.
Ethics Approval Statement: The study was conducted in compliance with the Declaration of Helsinki and approved by the COVID-19 scientific and ethics committee of the Leiden University Medical Center with number coco 2020-033. Furthermore a waiver for the requirement for informed consent was granted.
Suggested Citation: Suggested Citation