Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence

Abstract

Background Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients. Methods HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk factors for active SLE (SLEDAI score > 4) were identified by multiple logistic regression. Serum HCQ levels were measured in 68 additional patients known to be non-adherent, i.e. with whole-blood HCQ < 200 ng/mL. Results The mean (± SD) HCQ levels were 469 ± 223 ng/mL in serum and 916 ± 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 ± 0.15. In the multivariate analysis, low whole-blood HCQ levels (P = 0.023), but not serum HCQ levels, were independently associated with active SLE. From the mean serum/whole-blood level ratio, a serum HCQ level of 106 ng/mL was extrapolated as the corresponding cut-off to identify non-adherent patients with a sensitivity of 0.87 (95% CI 0.76–0.94) and specificity of 0.89 (95% CI 0.72–0.98). All serum HCQ levels of patients with whole-blood HCQ below the detectable level (< 20 ng/mL) were also undetectable (< 20 ng/mL). Conclusions These data suggest that whole blood is better than serum for assessing the pharmacokinetic/pharmacodynamic relation of HCQ. Our results support the use of serum HCQ levels to assess non-adherence when whole blood is unavailable.

Model informed dosing of hydroxycholoroquine in COVID‐19 patients: Learnings from the recent experience, remaining uncertainties and gaps

“…This model was also used for simulations of the serum concentrations serum PK data including data from 20 patients from the Gautret et al study 6 with a serum/whole blood correction ratio of 0.53 20 . The patients in the Gautret et al study were confirmed COVID‐19 and received 200 mg every 8 hours for 10 days.…”

Effects of hydroxychloroquine and its metabolites in patients with connective tissue diseases

“…However, one of the major shortcomings of these studies is the lack of validated methods for measuring blood levels of drugs and their metabolites, and the lack of comprehensive evaluation of the relationships between these levels and clinical parameters. Although a few studies in SLE, RA patients have shown that hydroxychloroquine as well as its metabolites have significant effects on treatment efficacy and adverse effects, there is no comprehensive study on this subject (Jallouli et al 2015b ; Omri et al 2020 ; Blanchet et al 2020 ; Carlsson et al 2020 ; Munster et al 2002 ).…”

Model informed dosing of Hydroxycholoroquine in COVID-19 patients: Learnings from the recent experience, remaining uncertainties and Gaps

“…Monte Carlo simulations were performed using NONMEM software, version 7.3 (Icon Development Solutions, Ellicott City, MD, USA). This model was also used for simulations of the serum concentrations serum PK data including data from 20 patients from Gautret et al study [6] with a serum/whole blood correction ratio of 0.53 [16]. Gautret et al study patients were confirmed COVID-19 and received 200 mg every 8 hours during 10 days.…”