Pharmacokinetics and pharmacodynamics profiles of enteric‐coated mycophenolate sodium in female patients with difficult‐to‐treat lupus nephritis
Abstract 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 (MP...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-07-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.13295 |
| _version_ | 1818517827235086336 |
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| author | Pajaree Chariyavilaskul Weeraya Phaisal Wonngarm Kittanamongkolchai Chutima Rukrung Sirirat Anutrakulchai Yingyos Avihingsanon |
| author_facet | Pajaree Chariyavilaskul Weeraya Phaisal Wonngarm Kittanamongkolchai Chutima Rukrung Sirirat Anutrakulchai Yingyos Avihingsanon |
| author_sort | Pajaree Chariyavilaskul |
| collection | DOAJ |
| description | Abstract 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‐AUC0–12h) ≥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 [Cmax], time to Cmax, and MPA‐AUC0–12h) 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‐AUC0–12h ≥45 μg.h/ml was best predicted by a single time point MPA concentration at C0.5, C2, C3, C4, and C8 (r2 = 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‐AUC0–12h ≥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. |
| first_indexed | 2024-12-11T01:01:33Z |
| format | Article |
| id | doaj.art-28c3c4f21b8d458c92efc925131266a0 |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-12-11T01:01:33Z |
| publishDate | 2022-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-28c3c4f21b8d458c92efc925131266a02022-12-22T01:26:18ZengWileyClinical and Translational Science1752-80541752-80622022-07-011571776178610.1111/cts.13295Pharmacokinetics and pharmacodynamics profiles of enteric‐coated mycophenolate sodium in female patients with difficult‐to‐treat lupus nephritisPajaree Chariyavilaskul0Weeraya Phaisal1Wonngarm Kittanamongkolchai2Chutima Rukrung3Sirirat Anutrakulchai4Yingyos Avihingsanon5Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Faculty of Medicine Chulalongkorn University Bangkok ThailandClinical Pharmacokinetics and Pharmacogenomics Research Unit, Faculty of Medicine Chulalongkorn University Bangkok ThailandMaha Chakri Sirindhorn Clinical Research Center Under the Royal Patronage, Research Affairs, Faculty of Medicine Chulalongkorn University Bangkok ThailandMaha Chakri Sirindhorn Clinical Research Center Under the Royal Patronage, Research Affairs, Faculty of Medicine Chulalongkorn University Bangkok ThailandDivision of Nephrology, Department of Medicine, Faculty of Medicine Khon Kaen University Knon Kaen ThailandRenal Immunology and Transplantation Research Unit Chulalongkorn University Bangkok ThailandAbstract 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‐AUC0–12h) ≥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 [Cmax], time to Cmax, and MPA‐AUC0–12h) 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‐AUC0–12h ≥45 μg.h/ml was best predicted by a single time point MPA concentration at C0.5, C2, C3, C4, and C8 (r2 = 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‐AUC0–12h ≥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.https://doi.org/10.1111/cts.13295 |
| spellingShingle | Pajaree Chariyavilaskul Weeraya Phaisal Wonngarm Kittanamongkolchai Chutima Rukrung Sirirat Anutrakulchai Yingyos Avihingsanon Pharmacokinetics and pharmacodynamics profiles of enteric‐coated mycophenolate sodium in female patients with difficult‐to‐treat lupus nephritis Clinical and Translational Science |
| title | Pharmacokinetics and pharmacodynamics profiles of enteric‐coated mycophenolate sodium in female patients with difficult‐to‐treat lupus nephritis |
| title_full | Pharmacokinetics and pharmacodynamics profiles of enteric‐coated mycophenolate sodium in female patients with difficult‐to‐treat lupus nephritis |
| title_fullStr | Pharmacokinetics and pharmacodynamics profiles of enteric‐coated mycophenolate sodium in female patients with difficult‐to‐treat lupus nephritis |
| title_full_unstemmed | Pharmacokinetics and pharmacodynamics profiles of enteric‐coated mycophenolate sodium in female patients with difficult‐to‐treat lupus nephritis |
| title_short | Pharmacokinetics and pharmacodynamics profiles of enteric‐coated mycophenolate sodium in female patients with difficult‐to‐treat lupus nephritis |
| title_sort | pharmacokinetics and pharmacodynamics profiles of enteric coated mycophenolate sodium in female patients with difficult to treat lupus nephritis |
| url | https://doi.org/10.1111/cts.13295 |
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