Ruiz: Hydroxychloroquine lung pharmacokinetics in critically ill patients infected with COVID-19 [HCQ]

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

Ruiz et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106247

Ruiz et al., Hydroxychloroquine lung pharmacokinetics in critically ill patients infected with COVID-19, International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106247

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HCQ lung pharmacokinetic study confirming that lung concentrations can be much higher than plasma and exceed predicted EC₅₀ values. The median lung epithelial lining fluid concentration was 38 times higher than plasma concentrations. 22 COVID-19 patients, median age 59.5.

Authors note that dosage determinations in studies assuming equilibrium between epithelium and plasma concentrations may lead to overly high dosages. Authors find the median ELF concentration of HCQ above the maximum EC₅₀ value for 400 mg x 1 /day and 200 mg x 3 /day, 7-12 days after treatment initiation.

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Ruiz et al., 28 Nov 2020, peer-reviewed, 14 authors.

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Abstract: International Journal of Antimicrobial Agents 57 (2021) 106247 Contents lists available at ScienceDirect International Journal of Antimicrobial Agents journal homepage: www.elsevier.com/locate/ijantimicag Hydroxychloroquine lung pharmacokinetics in critically ill patients with COVID-19 S. Ruiz a,∗, D. Concordet b, T. Lanot c, B. Georges a, P. Goudy a, S. Baklouti c, C. Mané c, E. Losha c, H. Vinour d, D. Rousset e, M. Lavit c, V. Minville a, J-M Conil a, P. Gandia b,c a CHU de Toulouse, Réanimation Polyvalente Hôpital Rangueil, Pôle d’Anesthésie-Réanimation, 1 avenue du Professeur Jean Poulhès, 31059, Toulouse cedex 9, France b INTHERES, Université de Toulouse, INRA, ENVT, 23 Chemin des Capelles, BP 87614, 31076, Toulouse cedex 3, France c CHU de Toulouse, Laboratoire de Pharmacocinétique et Toxicologie Clinique, Institut Fédératif de Biologie, 330 avenue de Grande-Bretagne, 31059, Toulouse cedex 9, France d CHU de Toulouse, Réanimation Polyvalente URM, Pôle d’Anesthésie-Réanimation, 330 avenue de Grande-Bretagne, 31059, Toulouse cedex 9, France e CHU de Toulouse, Réanimation Neurochirurgicale, Pôle d’Anesthésie-Réanimation, 330 avenue de Grande-Bretagne, 31059, Toulouse cedex 9, France a r t i c l e i n f o Article history: Received 17 June 2020 Accepted 22 November 2020 Keywords: COVID-19 Hydroxychloroquine Plasma drug monitoring Bronchoalveolar lavage BAL a b s t r a c t Different dosage regimens of hydroxychloroquine (HCQ) have been used to manage COVID-19 (coronavirus disease 2019) patients, with no information on lung exposure in this population. The aim of our study was to evaluate HCQ concentrations in the lung epithelial lining ﬂuid (ELF) in patients infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus that causes COVID-19. This was a retrospective, observational, multicentre, pharmacokinetic study of HCQ in critically ill COVID-19 patients. No additional interventions or additional samples compared with standard care of these patients were conducted in our teaching hospital. We included all intubated COVID-19 patients treated with crushed HCQ tablets, regardless of the dosage administered by nasogastric tube. Blood and bronchoalveolar lavage samples (n = 28) were collected from 22 COVID-19 patients and total HCQ concentrations in ELF were estimated. Median (interquartile range) HCQ plasma concentrations were 0.09 (0.06–0.14) mg/L and 0.07 (0.05–0.08) mg/L for 400 mg × 1/day and 200 mg × 3/day, respectively. Median HCQ ELF concentrations were 3.74 (1.10–7.26) mg/L and 1.81 (1.20–7.25) for 400 mg × 1/day and 200 mg × 3/day, respectively. The median ratio of ELF/plasma concentrations was 40.0 (7.3–162.7) and 21.2 (18.4–109.5) for 400 mg × 1/day and 200 mg × 3/day, respectively. ELF exposure is likely to be underestimated from HCQ concentrations in plasma. In clinical practice, low plasma concentrations should not induce an increase in drug dosage because lung exposure may already be high. © 2020 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

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