Pharmacokinetics of Enteric-Coated Mycophenolate Sodium in Lupus Nephritis (POEMSLUN)

Ranganathan, Dwarakanathan; Abdul‐Aziz, Mohd H.; John, George T.; McWhinney, Brett; Fassett, Robert G.; Healy, Helen; Kubler, Paul; Lim, Aaron; Lipman, Jeffrey; Purvey, Megan; Roberts, Matthew J.; Reyaldeen, Reza; Ungerer, Jacobus P.J.; Roberts, Jason A.

doi:10.1097/ftd.0000000000000658

Cited by 7 publications

(16 citation statements)

References 17 publications

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“…5 In a study comparing a fixed-dose or a concentration-controlled, EC-MPS dose was adjusted according to the clinical response or plasma MPA concentrations, and plasma MPA was crucial for achieving therapeutic response. 13 However, plasma MPA concentrations of both previous studies 5,13 tended to be low and were not steady for the whole study period; whereas in our study, average plasma MPA concentrations reached sustainable therapeutic levels until the 24-week time without any dose adjustment. Additionally, C0, C max , and MPA-AUC of EC-MPS in our study were higher than those in the previous reports, 5,13 confirming the use of 1440 mg/day as the optimum therapeutic dose of EC-MPS.…”

Section: Discussioncontrasting

confidence: 74%

Pharmacokinetics and pharmacodynamics profiles of enteric‐coated mycophenolate sodium in female patients with difficult‐to‐treat lupus nephritis

Chariyavilaskul

Phaisal

Kittanamongkolchai

et al. 2022

Clinical Translational Sci

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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. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?Therapeutic drug monitoring (TDM) is crucial in lupus nephritis (LN) treated with mycophenolic acid (MPA), especially mycophenolate mofetil. The area under the plasma concentration-time curve of MPA from time 0 to 12 h

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Section: Discussioncontrasting

confidence: 74%

Pharmacokinetics and pharmacodynamics profiles of enteric‐coated mycophenolate sodium in female patients with difficult‐to‐treat lupus nephritis

Chariyavilaskul

Phaisal

Kittanamongkolchai

et al. 2022

Clinical Translational Sci

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“…Previous studies have reported that MPA predose trough concentration ( C 0 ) correlates poorly with AUC [ 8 , 32 ]. In our study, the correlation coefficient between the AUC and C 0 is 0.304, which is consistent with the previously reported.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Enteric-Coated Mycophenolate Sodium in Children after Renal Transplantation and Initial Dosage Recommendation Based on Body Surface Area

Wang

Huang

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. Enteric-coated mycophenolate sodium (EC-MPS) is widely used in renal transplant recipients. There is a lack of study on the pharmacokinetics of this drug in children. This study is aimed at developing a population pharmacokinetic model of mycophenolic acid in children who were treated with EC-MPS after renal transplantation and to recommend initial dosage. Methods. Pediatric patients who had undergone renal transplantation and received EC-MPS were included. Data on demographic characteristics, biochemical tests, blood routine examinations, mycophenolic acid plasma concentrations, dosing amount and frequency of EC-MPS, and coadministered medications were retrospective collected from June 2018 to August 2019. Nonlinear mixed effect modeling methods were adopted to develop a population pharmacokinetic model with the data above. Additional data from September 2019 to July 2020 were used to validate the model. Simulations under different dosage regimen were conducted to evaluate the percentage of target attainment (PTA, AUC0-12h 30–60 mg·h/L). Results. A total of 96 pediatric patients aged at 13.3 (range 4.3–18.0) years were included in the modeling group. Data from 32 patients aged at 13.0 (range 3.6–18.3) years were used to validate the model. A one-compartment model with a double extravascular absorption was developed. Body surface area (BSA) was added as a covariate. Simulations showed that for different dosing regimens, the highest percentage of target attainment is around 50%. The best dosing regimen is 180 mg every 48 hours for patients with BSA of 0.22–0.46 m2, 180 mg every 24 hours with BSA of 0.47–0.67 m2, 180 mg every 24 hours with BSA of 0.68–0.96 m2, 360 mg every 24 hours with BSA of 0.97–1.18 m2, 540 mg every 24 hours with BSA of 1.19–1.58 m2, and 360 mg every 12 hours with BSA of 1.59–2.03 m2. Conclusion. BSA could affect the area under curve of mycophenolic acid with the administration of EC-MPS. Considering the inflexibility of the dosage form, future development of smaller amount per tablet suitable for younger children with BSA < 1.19 m 2 is warranted.

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“…To date, an adequate exposure dosage during initial treatment has not been fully established. [23][24][25] For these reasons, clinical pharmacists considered cyclophosphamide a suitable option, which was accepted by physicians. The patient was administered of 40 mg methylprednisolone daily, 0.6 g cyclophosphamide monthly and 0.1 g hydroxychloroquine twice daily.…”

Section: Induction Therapy and Maintenance Therapymentioning

confidence: 99%

Pharmacists’ role in multidisciplinary diagnosis and treatment in adverse reactions: A case report of interferon alfa-2b induced severe lupus

et al. 2022

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Rationale: Various side effects of interferon alfa-2b (IFN-α2b) have been reported. However, no relevant research has been conducted on the identification and treatment scheme selection for IFN-α2b induced severe systemic lupus erythematosus (SLE).Patient concerns: A 41-years-old man with a long history of hepatitis B who developed severe active SLE after IFN-α2b therapy for 24 months, with complete and persistent remission of clinical and laboratory abnormalities after IFN-α2b withdrawal, was not observed. Diagnosis:The patient was diagnosed with interferon-associated lupus by a multidisciplinary team involving pharmacists, and lupus nephritis by renal biopsy.Interventions: Methylprednisolone (40 mg/day) with intravenous cyclophosphamide (600 mg/body weight) was initiated and the symptoms were partially relieved. Cyclophosphamide was increased from 600 mg to 850 mg at the pharmacist's recommendation.Outcomes: The patient showed a favorable response to these therapies.Lessons: Clinical pharmacists collaborated with other members of the health care team to diagnose and treat adverse reactions, resulting in improved patient management.

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Pharmacokinetics of Enteric-Coated Mycophenolate Sodium in Lupus Nephritis (POEMSLUN)

Cited by 7 publications

References 17 publications

Pharmacokinetics and pharmacodynamics profiles of enteric‐coated mycophenolate sodium in female patients with difficult‐to‐treat lupus nephritis

Pharmacokinetics and pharmacodynamics profiles of enteric‐coated mycophenolate sodium in female patients with difficult‐to‐treat lupus nephritis

Population Pharmacokinetics of Enteric-Coated Mycophenolate Sodium in Children after Renal Transplantation and Initial Dosage Recommendation Based on Body Surface Area

Pharmacists’ role in multidisciplinary diagnosis and treatment in adverse reactions: A case report of interferon alfa-2b induced severe lupus

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