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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
Nov 2020  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
 
*, now with p < 0.00000000001 from 411 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19hcq.org
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.
Ruiz et al., 28 Nov 2020, peer-reviewed, 14 authors.
This PaperHCQAll
Hydroxychloroquine lung pharmacokinetics in critically ill patients with COVID-19
S Ruiz, D Concordet, T Lanot, B Georges, P Goudy, S Baklouti, C Mané, E Losha, H Vinour, D Rousset, M Lavit, V Minville, J-M Conil, P Gandia
International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106247
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.
Supplementary materials Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.ijantimicag.2020. 106247 .
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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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