ABSTRACT
Favipiravir is one of the repurposed antiviral medications for the treatment of SARS-CoV-2 infection. Since the dosing regimen is a prominent factor for the success of the antiviral therapy, this prospective observational study aimed to characterize the pharmacokinetic characteristics of favipiravir in COVID-19 patients. Adult patients (n=21) hospitalized for mild to moderate COVID-19 with a positive RT-PCR test, and assigned for favipiravir treatment were included. Favipiravir was administered for 5 days, with a loading dose of 3200 mg and a 1200 mg/day maintenance dose. Serial blood samples were collected on Day-2 and Day-4 of the therapy. Laboratory findings of the patients and in-hospital mortality were assessed. Favipiravir concentrations exhibited high variations and a significant decrease during the treatment of COVID-19. The median favipiravir trough concentration (C0-trough) on Day-2 was 21.26 µg/mL whereas it decreased significantly to 1.61 µg/mL on Day-4, the area under the concentration versus time curve decreased from 345.6 µg.h/mL to 108.6 µg.h/mL, respectively. Gender seems significant to affect favipiravir concentrations. Day-2-C0-trough of female patients was significantly higher than male patients. Of the 5 patients that died, 4 were male with a significant increase in ferritin levels from Day-0 to Day-5 compared to surviving patients. In addition, there was a significant decrease in D-dimer and CRP levels in the surviving patients. Our findings indicate that favipiravir concentrations show significant changes during the treatment of COVID-19. Therapeutic drug monitoring may best guide dose adjustments in patients that do not respond to treatment with favipiravir.
Subject(s)
COVID-19ABSTRACT
Background Coronavirus disease 2019 (COVID-19) quickly spread worldwide to become a pandemic. This study aimed to define the predictors of critical illness development within 28 days postadmission. Methods We conducted a prospective cohort study including 477 PCR-positive COVID-19 patients admitted to a tertiary care hospital in Istanbul from March 12 to May 12, 2020. The development of critical illness, e.g., invasive mechanical ventilation and/or death, was followed for a period of 28 days postadmission. Demographic characteristics, number of comorbidities, illness severity at admission defined by the WHO scale, vital signs, laboratory findings and period of admission to the hospital were independent variables. Cox proportional hazards analysis was performed, and the C-index was calculated. Results The median (IQR) age of the cohort was 55.0 (44.0-67.0) years, and 50.1% were male. The most common presenting symptoms were cough, dyspnea and fatigue. Overall, 65.2% of the patients had at least one comorbidity. Hydroxychloroquine was given to 99.2% of the patients. Critical illness developed in 45 (9.4%; 95% CI: 7.0%-12.4%) patients. In the multivariable analysis, age (HR: 1.05, p<0.001), number of comorbidities (HR: 1.33, p=0.02), procalcitonin [≥]0.25 g/L (HR: 2.12, p=0.03) and LDH [≥]350 U/L (HR: 2.04, p=0.03) were independently associated with critical illness development. The WHO scale on admission was the strongest predictor of critical illness (HR: 4.15, p<0.001). Prognosis improved within the study period (p<0.05). The C-index of the model was 0.92. Conclusions Age, comorbidity number, WHO scale, LDH and procalcitonin were independently associated with critical illness development. Mortality from COVID-19 seems to be decreasing as the pandemic advances.