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Genotype-guided new approach for dose optimisation of hydroxychloroquine administration in Chinese patients with SLE.
Xie, Han; Wen, Xin; Wang, Yuchun; Huang, Xuan; Shu, Qing; Wang, Dandan; Geng, Linyu; Jin, Ziyi; Shen, Wei; Ge, Weihong; Zhu, Yizhun; Sun, Lingyun.
Afiliación
  • Xie H; School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau SAR, China.
  • Wen X; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China.
  • Wang Y; Department of Pharmacy, Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China.
  • Huang X; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China.
  • Shu Q; School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau SAR, China.
  • Wang D; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China.
  • Geng L; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, China.
  • Jin Z; Department of Pharmacy, Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China.
  • Shen W; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China.
  • Ge W; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China.
  • Zhu Y; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China.
  • Sun L; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China.
Lupus Sci Med ; 10(2)2023 11 22.
Article en En | MEDLINE | ID: mdl-37993281
ABSTRACT

OBJECTIVES:

The study aims to investigate the impact of gene polymorphisms on blood hydroxychloroquine (HCQ) concentrations in patients with SLE and provide guidelines for individualised care.

METHODS:

489 Chinese patients with SLE taking HCQ for more than 3 months were collected in this study. The blood HCQ, desethylhydroxychloroquine (DHCQ) and desethylchloroquine concentrations were measured. The optimal blood concentration of HCQ was determined by receiver operating characteristic curve analysis. Single nucleotide polymorphisms of metabolic enzymes involved in HCQ metabolism were genotyped and the associations with treatment effects were investigated.

RESULTS:

The cut-off value of HCQ was 559.67 ng/mL, with sensitivity and specificity values of 0.51 and 0.89, respectively. The TC and CC genotypes of CYP2C8 (rs7910936) were significantly related to the increase in blood HCQ concentrations, and the CYP2C8 (rs10882521) TT genotype was associated with lower blood HCQ concentrations. The DHCQHCQ ratio was highest in patients with the GG genotype of the CYP2D6*10 (rs1065852) polymorphism and lowest in those with the AA genotype. Patients with the CYP2C8 (rs7910936) CC genotype were more likely to achieve the optimal blood concentration (p=0.030) in HCQ 200 mg/day group and patients with the CYP2D6*10 (rs1065852) GG genotype were more likely to reach the optimal blood concentration (p=0.049) in 400 mg/day group.

CONCLUSIONS:

Our results suggest that the optimal blood concentration of HCQ measured approximately 12-18 hours after the last dosage may be between 500 and 600 ng/mL in Chinese patients with SLE. The observed variations in HCQ concentrations between individuals can potentially be attributed to genetic polymorphisms in CYP2D6*10 (rs1065852) and CYP2C8 (rs7910936 and rs10882521). Genotypical testing of patients and regular monitoring of blood levels are recommended for optimising HCQ dosage management in Chinese patients with SLE. TRIAL REGISTRATION NUMBER ChiCTR2300070628.
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Texto completo: 1 Colección: 01-internacional Asunto principal: Antirreumáticos / Lupus Eritematoso Sistémico Límite: Humans Idioma: En Revista: Lupus Sci Med Año: 2023 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Asunto principal: Antirreumáticos / Lupus Eritematoso Sistémico Límite: Humans Idioma: En Revista: Lupus Sci Med Año: 2023 Tipo del documento: Article País de afiliación: China