title: Factors Related to Blood Hydroxychloroquine Concentration in Patients With Systemic Lupus Erythematosus.
abstract: To identify factors associated with blood concentrations of hydroxychloroquine (HCQ) and its major metabolite, N-desethylhydroxychloroquine (DHCQ), in patients with systemic lupus erythematosus (SLE; lupus) receiving long-term oral HCQ treatment.
  
  
  
  SLE patients who had been taking HCQ for more than 3 months were recruited. Various clinical characteristics, laboratory values, and SLE Disease Activity Index (SLEDAI) scores were examined. The concentrations of HCQ and DHCQ ([HCQ] and [DHCQ]) were measured by liquid chromatography mass spectrometry, and the relationship between [HCQ], [DHCQ], and [HCQ]:[DHCQ] ratio to various factors was investigated.
  
  
  
  In total, 189 SLE patients receiving long-term HCQ treatment were included in the analysis. The median (interquartile range [IQR]) [HCQ] was 515 (IQR 353-720) ng/ml, the median [DHCQ] was 417 (IQR 266-591) ng/ml, and the median [HCQ]:[DHCQ] ratio was 1.3 (range 1.0-1.7). [HCQ] was closely associated with [DHCQ] (r = 0.81, P < 0.0001). The weight-adjusted oral HCQ dose was strongly associated with both [HCQ] (P < 0.001) and [DHCQ] (P < 0.001). Time since last dose was associated with [HCQ] (P < 0.001). No statistically significant association was found between renal function or smoking and [HCQ] or [DHCQ]. Use of additional immunosuppressants increased both [HCQ] and [DHCQ] after adjusting for possible confounders (P = 0.04 and P = 0.03, respectively). The lower SLEDAI score was significantly related to higher [HCQ], after adjusting for age, sex, weight-adjusted HCQ dose, time since last dose, number of other immunosuppressants, and smoking status (P = 0.007).
  
  
  
  Various factors affected blood levels of [HCQ], [DHCQ], or the [HCQ]:[DHCQ] ratio of SLE patients receiving long-term oral HCQ treatment. Notably, higher [HCQ] was associated with a lower SLEDAI score in our typical outpatient clinic population with lupus.
authors.affiliation: Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, South Korea.
authors.forename: Ji
authors.initials: J
authors.lastname: Yeon Lee
authors.affiliation: Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, South Korea.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lee
authors.affiliation: Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, South Korea.
authors.forename: Seung
authors.initials: S
authors.lastname: Ki Kwok
authors.affiliation: Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, South Korea.
authors.forename: Ji
authors.initials: J
authors.lastname: Hyeon Ju
authors.affiliation: Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, South Korea.
authors.forename: Kyung
authors.initials: K
authors.lastname: Su Park
authors.affiliation: Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, South Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
mesh_terms: D000284:Administration, Oral; D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood* / Q000493:pharmacokinetics; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D006886:Hydroxychloroquine; C049283:cletoquine