Evaluation of Hydroxychloroquine Blood Concentrations and Effects in Childhood-Onset Systemic Lupus Erythematosus
Background: Hydroxychloroquine (HCQ) is an antimalarial agent given to patients with systemic lupus erythematosus (SLE) as first-line therapy. It alleviates childhood-onset systemic lupus erythematosus cSLE skin and musculoskeletal disease, decreasing disease activity and flares. HCQ concentration-e...
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| Auteurs principaux: | , , , , , , , , |
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| Format: | Livre |
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MDPI AG,
2021-03-01T00:00:00Z.
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| Résumé: | Background: Hydroxychloroquine (HCQ) is an antimalarial agent given to patients with systemic lupus erythematosus (SLE) as first-line therapy. It alleviates childhood-onset systemic lupus erythematosus cSLE skin and musculoskeletal disease, decreasing disease activity and flares. HCQ concentration-effect relationships in children remains unknown. This study aimed to investigate the pharmacokinetics of HCQ and possible concentration-effect relationships. Methods: HCQ blood concentrations and effects were obtained during clinical follow-up on different occasions. cSLE flares were defined using the SLE Disease Activity Index (SLEDAI); flare was denoted by a SLEDAI score > 6. Blood concentration was measured using high-performance liquid chromatography with fluorometric detection. Statistical analysis was performed using a nonlinear mixed-effect approach with the Monolix software. Results: A total of 168 blood samples were obtained from 55 pediatric patients. HCQ apparent blood clearance (CL/F) was dependent on patients' bodyweight and platelet count. Patients with active cSLE had a lower mean blood HCQ concentration compared with inactive cSLE patients (536 ± 294 vs. 758 ± 490 ng/mL, <i>p</i> = 5 × 10<sup>−6</sup>). Among patients with HCQ blood concentration ≥750 ng/mL, 87.6% had inactive cSLE. Moreover, HCQ blood concentration was a significant predictor of disease status. Conclusion: We developed the first HCQ blood concentration-effect relationship for cSLE associated with active or non-active disease status. A prospective randomized study is necessary to confirm these results. |
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| Description: | 10.3390/ph14030273 1424-8247 |