Open AccessPharmacokinetics and pharmacodynamics profiles of enteric‐coated mycophenolate sodium in female patients with difficult‐to‐treat lupus nephritis
Author(s) -
Chariyavilaskul Pajaree,
Phaisal Weeraya,
Kittanamongkolchai Wonngarm,
Rukrung Chutima,
Anutrakulchai Sirirat,
Avihingsa Yingyos
Publication year - 2022
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.13295
Subject(s) - cmax , mycophenolic acid , pharmacokinetics , pharmacodynamics , pharmacology , mycophenolate , imp dehydrogenase , lupus nephritis , dosing , chemistry , therapeutic drug monitoring , medicine , creatinine , urology , transplantation , disease
Relapsed or resistant lupus nephritis (LN) is considered a difficult‐to‐treat type of LN, and enteric‐coated mycophenolate sodium (EC‐MPS) has been used in this condition. Therapeutic drug monitoring using the area under the plasma mycophenolic acid concentration from 0 to 12 h postdose (MPA‐AUC 0–12h ) ≥45 μg.h/ml is a useful approach to achieve the highest efficiency. This study assessed EC‐MPS’s pharmacokinetic (PK) and pharmacodynamic (PD) profiles and investigated an optimal level of the single time point of plasma MPA concentration. Nineteen biopsy‐proven patients with class III/IV LN received 1440 mg/day of EC‐MPS for 24 weeks. PK (maximum plasma MPA concentration [ C max ], time to C max , and MPA‐AUC 0–12h ) and PD (activity of inosine‐5′‐monophosphate dehydrogenase [IMPDH]) parameters were measured at weeks 2, 8, 16, and 24. We found that IMPDH activity decreased from baseline by 31–42% within 2–4 h after dosing, coinciding with the increased plasma MPA concentration. MPA‐AUC 0–12h ≥45 μg.h/ml was best predicted by a single time point MPA concentration at C0.5, C2, C3, C4, and C8 ( r 2 = 0.516, 0.514, 0.540, 0.611, and 0.719, respectively), independent of dose, albumin, urine protein/creatinine ratio, and urinalysis. The MPA‐C0.5 cutoff of 2.03 g/ml yielded the highest overall sensitivity of 85% and specificity of 88.2% in predicting MPA‐AUC 0–12h ≥45 μg.h/ml. A single timepoint of plasma MPA‐C0.5 ≥2.03 μg/ml may help guide EC‐MPS adjustment to achieve adequate drug exposure. Further study of EC‐MPS used to validate this cutoff is warranted.