Systemic exposure to hydroxychloroquine and its relationship with outcome in severely ill COVID-19 patients in New York City.
Br J Clin Pharmacol
; 89(1): 299-315, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-35961374
ABSTRACT
AIM:
To investigate the relationship between systemic exposure to hydroxychloroquine (HCQ) and its metabolite desethylhydroxychloroquine (DHCQ) and clinical outcome in severely ill patients treated with a standard oral dose regimen of HCQ during the first wave of COVID-19 in New York City.METHODS:
We correlated retrospective clinical data with drug exposure prospectively assessed from convenience samples using population pharmacokinetics and Bayesian estimation. Systemic exposure was assessed in 215 patients admitted to ICU or COVID-ward for whom an interleukin-6 level was requested and who were still alive 24 hours after the last dose of HCQ. Patients received oral HCQ 600 mg twice daily on day 1 followed by 4 days of 400 mg daily.RESULTS:
Fifty-three precent of the patients were intubated at 5.4 ± 6.4 days after admission and 26.5% died at an average of 32.2 ± 19.1 days. QTc at admission was 448 ± 34 ms. Systemic exposure to HCQ and DHCQ demonstrated substantial variability. Cumulative area under the serum concentration-time curve up to infinity for HCQ was 71.4 ± 19.3 h mg/L and for DHCQ 56.5 ± 28.3 h mg/L. Variability in systemic exposure was not clearly explained by renal function, liver function or inflammatory state. In turn, systemic exposure did not correlate with intubation status, survival or QTc prolongation.CONCLUSION:
This study in severely ill patients was not able to find any relationship between systemic exposure to HCQ and DHCQ and clinical outcome at a routine dose regimen and adds to the growing body of evidence that oral HCQ does not alter the course of disease in COVID-19 patients.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
COVID-19
/
Hidroxicloroquina
Limite:
Humans
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Br J Clin Pharmacol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos