M Jallouli1, L Galicier2, N Zahr3, O Aumaître4, C Francès5, V Le Guern1, F Lioté6, A Smail7, N Limal8, L Perard9, H Desmurs-Clavel9, D Le Thi Huong10, B Asli2, J-E Kahn11, J Pourrat12, L Sailler13, F Ackermann11, T Papo14, K Sacré14, O Fain15, J Stirnemann16, P Cacoub17, G Leroux10, J Cohen-Bittan18, J Sellam19, X Mariette20, B Blanchet21, J S Hulot3, Z Amoura10, J C Piette10, N Costedoat-Chalumeau1. 1. Université Paris-Descartes, AP-HP, Hôpital Cochin, and Centre de Référence Maladies Auto-Immunes et Systémiques Rares, Paris, France. 2. Université Paris Diderot, Sorbonne Paris Cité, and AP-HP, Hôpital Saint Louis, Paris, France. 3. Université Pierre et Marie Curie and AP-HP, Hôpital Pitié-Salpêtrière, Paris, France. 4. Université de Clermont-Ferrand and Centre Hospitalier Universitaire (CHU) Clermont-Ferrand, Hôpital Gabriel Montpied, Clermont-Ferrand, France. 5. Université Pierre et Marie Curie and AP-HP, Hôpital Tenon, Paris, France. 6. Université Paris Diderot, Sorbonne Paris Cité, and AP-HP, Hôpital Lariboisière, Paris, France. 7. CHU Amiens, Hôpital Nord, Amiens, France. 8. AP-HP, Hôpital Henri Mondor, Créteil, France. 9. Hospices Civils de Lyon, Groupement Hospitalier Edouard Herriot, Lyon, France. 10. Université Pierre et Marie Curie, AP-HP, Hôpital Pitié-Salpêtrière, and Centre de Référence pour le Lupus Systémique et le Syndrome des Antiphospholipides, Paris, France. 11. Université Versailles St. Quentin en Yvelines and Hôpital Foch, Suresnes, France, and Université Paris-Sud and AP-HP, Hôpitaux Universitaires Paris-Sud, Le Kremlin Bicêtre, France. 12. Université Paul Sabatier and CHU Toulouse, Hôpital Rangueil, Toulouse, France. 13. Université Paul Sabatier and CHU Toulouse, Hôpital Purpan, Toulouse, France. 14. Université Paris Diderot, Sorbonne Paris-Cité, and AP-HP, Hôpital Bichat Claude-Bernard, Paris, France. 15. Université Pierre et Marie Curie, Inflammation Immunopathology Biotherapy Department, and AP-HP, Hôpital St. Antoine, Paris, France. 16. Geneva University Hospital, Geneva, Switzerland. 17. Sorbonne Universités, Université Pierre et Marie Curie, UMR 7211, and Inflammation Immunopathology Biotherapy Department, AP-HP, Hôpital Pitié-Salpêtrière, Centre de Référence pour le Lupus Systémique et le Syndrome des Antiphospholipides, INSERM UMRS 959, and CNRS, FRE3632, Paris, France. 18. AP-HP, Hôpital Pitié-Salpêtrière, Paris, France. 19. AP-HP, Université Pierre et Marie Curie, Inflammation Immunopathology Biotherapy Department, and INSERM UMRS 938, Paris, France. 20. Université Paris-Sud, INSERM U1012, and AP-HP, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. 21. AP-HP, Hôpital Cochin, Paris, France.
Abstract
OBJECTIVE: Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations. METHODS: We conducted a retrospective analysis of patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to determine the association of epidemiologic, clinical, and biologic factors with blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration <200 ng/ml) were excluded. RESULTS: To examine homogeneous pharmacologic data, we restricted the analyses of the PLUS data to the 509 SLE patients receiving 400 mg/day. We found no association of ethnicity or smoking with blood HCQ concentrations and no pharmacokinetic drug-drug interaction with antacids or with inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index (P = 0.008), no treatment with corticosteroids (P = 0.04), increased time between the last tablet intake and measurement of blood HCQ concentrations (P = 0.017), low platelet count (P < 0.001), low neutrophil count (P < 0.001), and high estimated creatinine clearance (P < 0.001) were associated with low blood HCQ concentrations. In 22 SLE patients with chronic renal insufficiency (median serum creatinine clearance 52 ml/minute [range 23-58 ml/minute]) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than that in the 509 patients from the PLUS study (1,338 ng/ml [range 504-2,229 ng/ml] versus 917 ng/ml [range 208-3316 ng/ml]) (P < 0.001). CONCLUSION: We provide a comprehensive analysis of determinants of blood HCQ concentrations. Because this measurement is increasingly being used, these data might be useful for clinicians.
OBJECTIVE: Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations. METHODS: We conducted a retrospective analysis of patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to determine the association of epidemiologic, clinical, and biologic factors with blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration <200 ng/ml) were excluded. RESULTS: To examine homogeneous pharmacologic data, we restricted the analyses of the PLUS data to the 509 SLEpatients receiving 400 mg/day. We found no association of ethnicity or smoking with blood HCQ concentrations and no pharmacokinetic drug-drug interaction with antacids or with inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index (P = 0.008), no treatment with corticosteroids (P = 0.04), increased time between the last tablet intake and measurement of blood HCQ concentrations (P = 0.017), low platelet count (P < 0.001), low neutrophil count (P < 0.001), and high estimated creatinine clearance (P < 0.001) were associated with low blood HCQ concentrations. In 22 SLEpatients with chronic renal insufficiency (median serum creatinine clearance 52 ml/minute [range 23-58 ml/minute]) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than that in the 509 patients from the PLUS study (1,338 ng/ml [range 504-2,229 ng/ml] versus 917 ng/ml [range 208-3316 ng/ml]) (P < 0.001). CONCLUSION: We provide a comprehensive analysis of determinants of blood HCQ concentrations. Because this measurement is increasingly being used, these data might be useful for clinicians.
Authors: Byeong Yun Ahn; Chang Kyung Kang; Jong Do Seo; Pyoeng Gyun Choe; Sang Hoon Song; Wan Beom Park; Sang Won Park; Nam Joong Kim; Myoung Don Oh Journal: J Korean Med Sci Date: 2020-06-22 Impact factor: 2.153
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