Determination of the concentration of hydroxychloroquine and its metabolites in peripheral blood of systemic lupus erythematosus patients and its clinical significance
10.3760/cma.j.cn141217-20210830-00342
- VernacularTitle:系统性红斑狼疮患者外周血羟氯喹及其代谢产物血浓度检测及临床意义的初步探讨
- Author:
Xinchen PENG
1
;
Menglu PAN
;
Junnan XU
;
Yue LIU
;
Zongwen SHUAI
Author Information
1. 安徽医科大学第一附属医院风湿免疫科，合肥 230032
- Keywords:
Hydroxychloroquine;
Lupus erythematosus, systemic;
Metabolites;
Blood concentration;
Factors
- From:
Chinese Journal of Rheumatology
2022;26(2):79-86
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate factors associated with the concentration of hydroxychloroquine (HCQ) and its metabolites in peripheral blood of patients with systemic lupus erythematosus (SLE) who were receiving long-term oral HCQ treatment.Methods:SLE patients who had been taking HCQ for more than 3 months were recruited. Clinical characteristics, laboratory test results and SLE disease activity index (SLEDAI) scores were examined. The concentrations of HCQ and its metabolites from peripheral blood were measured by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Student's-test and Nonpara-metric tests were used to compare quantitative data, Chi-square and Fisher's exact tests were used to analyze qualitative data. Correlation between the test results was assessed by correlation coefficient. Variables with P values less than 0.05 in univariate analysis were entered into a logistic regression model. Results:In total, 191 SLE patients on long-term HCQ treatment were included in the analysis. Medians of HCQ blood concentrations ([HCQ]), desethylhydroxychloroquine (DHCQ) blood concentrations ([DHCQ]), desethylchloroquine (DCQ) blood concentrations ([DCQ]) and bisdesethylchloroquine (BDCQ) blood concentrations ([BDCQ]) were 523.19 (402.63, 677.88) ng/ml, 291.79 (212.30, 432.51) ng/ml, 49.37 (35.00, 73.05) ng/ml, 21.78(14.37, 52.46) ng/ml respectively. On multivariate analysis, weight-adjusted oral HCQ dose [ OR(95% CI)=1.366 (1.053, 1.772) , P=0.019], the course of hydroxychloroquine [ OR (95% CI) =0.991 (0.984, 0.999), P=0.026], estimated glomerular filtration rate [ OR(95% CI)=0.984 (0.971, 0.997), P=0.014] and platelet count [ OR (95% CI)=1.010 (1.005, 1.015), P<0.001] were associated with [HCQ]. [HCQ], [DCQ], [BDCQ], [BDCQ]/[HCQ] were negatively correlated with estimated glomerular filtration rate (eGFR) ( r=-0.20, P=0.006; r=-0.19, P=0.010; r=-0.26, P<0.001; r=-0.15, P=0.044, respectively) after adjusted for age, course of disease, duration of HCQ treatment and weight adjusted HCQ dosage, [DHCQ]/[HCQ] was negatively correlated with the SLEDAI score ( r=-0.16, P=0.027) when the effects of glucocorticoid was controlled, [BDCQ]/[HCQ] among different renal function levels was statistically significant ( H=12.46, P=0.014). Conclusion:The factors associated with HCQ blood concentrations in SLE patients on long-term oral HCQ treatment are weight-adjusted HCQ dosage, duration of hydroxychloroquine intake and renal function. In addition, [BDCQ] is closely correlated with renal function, [DHCQ] is correlated with SLE disease activity.
