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Purpose <p>Mycophenolate mofetil (MMF) is widely used in lupus nephritis (LN), but interindividual variability in pharmacokinetics and pharmacogenetics may affect treatment response. This study investigated the relationship between MMF pharmacokinetics, key genetic polymorphisms, and therapeutic response in Egyptian female LN patients.</p> Methods and results <p>In this prospective study, 53 female patients with active LN (ISN/RPS class III–IV) maintained on 2&#xa0;g/day MMF were enrolled at the Urology and Nephrology Center, Mansoura University, Egypt. Baseline clinical, laboratory, and histopathological data were collected. Serial blood samples were obtained over 8&#xa0;h for mycophenolic acid (MPA) quantification by LC/MS. Genomic DNA was extracted for UGT2B7 (rs7438135) and SLCO1B1 (rs183624077) genotyping using TaqMan real-time PCR assays. Treatment response was classified as complete or partial remission versus non-response at 6 months. Population pharmacokinetics were analyzed using Monolix 2020R1. Considerable variability in MPA exposure was observed (mean AUC₀–₈: 22.4 ± 12.9&#xa0;µg·h/mL; mean Cmax: 12.9 ± 5.5&#xa0;µg/mL). Responders exhibited higher median AUC₀–₈ than non-responders (23.1 vs. 16.2&#xa0;µg·h/mL; <i>p</i> = 0.039). SLCO1B1 and UGT2B7 genotypes did not differ significantly between responders and non-responders, though TT carriers showed lower MPA AUC₀–₈. Multivariate analysis identified biopsy class (III vs. IV), induction therapy with MMF, and higher MPA AUC₀–₈ as independent predictors of response.</p> Conclusions <p>MMF exposure, biopsy class, and induction regimen significantly influence therapeutic response in LN. Pharmacokinetic monitoring of MPA may help optimize MMF therapy, while common UGT2B7 and SLCO1B1 variants showed limited predictive value in this cohort.</p>

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Pharmacogenetics and pharmacokinetics of immunosuppressants: clinical correlations and disease activity control in Egyptian female patients with lupus nephritis

  • 期刊论文

  • 发表日期：

    2026年5月16日

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  • Ahmed Yahia Elmowafy,
  • Salwa Elwasif,
  • Rasha Shemies,
  • Ahmed Mansour Abdel-Rahman,
  • Mahmoud M. Zakaria,
  • Sameha A. Omar,
  • Randa El-Gamal,
  • Nehal M. Ramadan,
  • Hala Abdel Malek

摘要

Purpose

Mycophenolate mofetil (MMF) is widely used in lupus nephritis (LN), but interindividual variability in pharmacokinetics and pharmacogenetics may affect treatment response. This study investigated the relationship between MMF pharmacokinetics, key genetic polymorphisms, and therapeutic response in Egyptian female LN patients.

Methods and results

In this prospective study, 53 female patients with active LN (ISN/RPS class III–IV) maintained on 2 g/day MMF were enrolled at the Urology and Nephrology Center, Mansoura University, Egypt. Baseline clinical, laboratory, and histopathological data were collected. Serial blood samples were obtained over 8 h for mycophenolic acid (MPA) quantification by LC/MS. Genomic DNA was extracted for UGT2B7 (rs7438135) and SLCO1B1 (rs183624077) genotyping using TaqMan real-time PCR assays. Treatment response was classified as complete or partial remission versus non-response at 6 months. Population pharmacokinetics were analyzed using Monolix 2020R1. Considerable variability in MPA exposure was observed (mean AUC₀–₈: 22.4 ± 12.9 µg·h/mL; mean Cmax: 12.9 ± 5.5 µg/mL). Responders exhibited higher median AUC₀–₈ than non-responders (23.1 vs. 16.2 µg·h/mL; p = 0.039). SLCO1B1 and UGT2B7 genotypes did not differ significantly between responders and non-responders, though TT carriers showed lower MPA AUC₀–₈. Multivariate analysis identified biopsy class (III vs. IV), induction therapy with MMF, and higher MPA AUC₀–₈ as independent predictors of response.

Conclusions

MMF exposure, biopsy class, and induction regimen significantly influence therapeutic response in LN. Pharmacokinetic monitoring of MPA may help optimize MMF therapy, while common UGT2B7 and SLCO1B1 variants showed limited predictive value in this cohort.