Hydroxychloroquine lung pharmacokinetics in critically ill patients infected with COVID-19.

Different dosage regimens of hydroxychloroquine were used to manage COVID-19 patients, with no information on the lungs' exposure in this population. The aim of our study was to evaluate hydroxychloroquine concentrations in the lung epithelial lining fluid (ELF) in patients infected with COVID-19. This study is a retrospective, observational, multicenter, pharmacokinetics study of hydroxychloroquine in critically ill patients. No additional interventions or additional samples compared to standard care of these patients were conducted in our teaching hospital. We included all intubated COVID-19 patients treated with crushed hydroxychloroquine tablets, regardless of the dosage administered by the nasogastric tube. Blood and bronchoalveolar lavage (BAL) samples (n= 28) were collected from 22 COVID-19 patients and the total hydroxychloroquine concentrations in epithelial lining fluid were estimated. Median hydroxychloroquine plasma concentrations were of 0.09 [0.06; 0.14] mg/l and 0.07 [0.05; 0.08] mg/l for 400 mg x 1/day and 200 mg x 3/day, respectively. Median hydroxychloroquine ELF concentrations were of 3.74 [1.10; 7.26] mg/l and 1.81 [1.20; 7.25] for 400 mg x 1/day and 200 mg x 3/day, respectively. The median ratio of ELF/plasma concentrations was of 40.0 [7.3; 162.7] and 21.2 [18.4; 109.5] for 400 mg x 1/day and 200 mg x 3/day, respectively. Exposure in the ELF is likely to be underestimated due to the concentrations of plasma hydroxychloroquine. In clinical practice, low plasma concentrations should not induce an increase in drug dosage because the lung exposure may already be high.