Pharmacokinetics of mycophenolic acid in severe lupus nephritis

Lertdumrongluk, Paungpaga; Somparn, Poorichaya; Kittanamongkolchai, Wonngarm; Traitanon, Opas; Vadcharavivad, Somratai; Avihingsanon, Yingyos

doi:10.1038/ki.2010.170

Cited by 73 publications

(85 citation statements)

References 32 publications

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“…The finding of higher total MPA AUC(0,12 h) in all responders is consistent with the results of a previous investigation involving patients with lupus nephritis (65.98 ± 23.77 vs. 32.08 ± 7.97 mg l -1 h) [8]. A significantly higher total MPA AUC(0,8 h) was also observed in all responders.…”

Section: Discussionsupporting

confidence: 81%

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Exposure–effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis

Rahman

Tett

Gafor

et al. 2015

Brit J Clinical Pharma

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AIMSThe aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis. METHODSSix blood samples were drawn pre-and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C 0 ), maximum concentration (C max ) and area under the concentration-time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drugrelated adverse events. [7][8][9][10][11][12][13][14][15][16][17][18][19] was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023). RESULTS Dose CONCLUSIONSThis study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis.

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Section: Discussionsupporting

confidence: 81%

“…The analyses evaluated drug exposures in relation to treatment response since starting MPA and drugrelated adverse events. [7][8][9][10][11][12][13][14][15][16][17][18][19] was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023). …”

mentioning

confidence: 83%

Exposure–effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis

Rahman

Tett

Gafor

et al. 2015

Brit J Clinical Pharma

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“…As exposure to prednisone and MF was comparable between the two groups of patients, dose does not seem to affect the responses. Pharmacokinetic monitoring of mycophenolic acid has traditionally received little attention; however, findings in this area have recently become available [33]. Therefore, most participating centers in our study did not monitor serum levels.…”

Section: Discussionmentioning

confidence: 99%

Mycophenolate as Induction Therapy in Lupus Nephritis with Renal Function Impairment

Rivera

Fulladosa²,

Poveda³

et al. 2012

Am J Nephrol

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Background: Mycophenolate (MF) is effective as induction therapy for lupus nephritis (LN) in patients with normal renal function; however, little is known about its role in patients with impaired renal failure. The purpose of this study was to evaluate the response to MF in LN and its association with baseline renal function. Methods: Data were obtained for 90 patients from 12 Spanish renal units who were receiving MF as induction therapy for LN. Patients were classified into 2 groups: group 1 (estimated glomerular filtration rate [eGFR] ≥60 ml/min/1.73 m²) and group 2 (eGFR <60 ml/min/ 1.73 m²). The primary outcome measure was the percentage of patients who achieved any response and its relationship with initial eGFR. The secondary outcome measures were the percentage of patients who achieved a complete response (CR) or partial response (PR) and the appearance of relapses during treatment and side effects. Results: At initiation of MF treatment, there were no differences in the main parameters between group 1 (n = 63; eGFR 87 ± 23 ml/min/ 1.73 m²) and group 2 (n = 27; eGFR 44 ± 12 ml/min/1.73 m²). Exposure to prednisone and MF was similar. The percentages of patients who achieved a response in groups 1 and 2 were, respectively, 69.2 and 43.8% at 6 months and 81.3 and 73.7% at 12 months. CR was more frequent in group 1, whereas PR was similar in both groups. Four patients relapsed and side effects were unremarkable. Conclusions: MF is effective and safe as induction therapy for LN, and response is even achieved in patients with baseline renal impairment.

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“…The results also highlighted the importance of socioeconomic issues in health care access and delivery in Asian countries. Also, studies in Thai patients have shown that there was a marked interindividual difference in MPA metabolism and that drug exposure was related to therapeutic response [73,74]. In this regard, there are ongoing studies on the pharmacokinetics and pharmacogenomics of MPA in different Asian populations.…”

Section: Discussionmentioning

confidence: 99%

Lupus Nephritis in Asia: Clinical Features and Management

Yap

Chan²

2015

Kidney Dis

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Background: Lupus nephritis (LN) is a common and severe organ involvement manifesting itself in systemic lupus erythematosus (SLE). There is a considerable difference in prevalence, severity, treatment response and outcomes between Asian LN patients and LN patients from other racial backgrounds. Summary: Asian SLE patients have a higher prevalence of LN than Caucasian SLE patients and often present with a more severe disease. Increasing data from genetic studies, accompanied by progress in high-throughput genotyping, have advanced our knowledge about genetic predispositions that might partly contribute to the clinical variations observed. Corticosteroids combined with either cyclophosphamide (CYC) or mycophenolic acid (MPA) is the current standard-of-care induction regimen for severe LN irrespective of race or ethnicity. However, the preference for MPA or CYC, and possibly the optimum dose for MPA, is influenced by the patient's origin. Also, there is an insufficient evidence base for reduced-dose intravenous CYC in Asian patients. Health economics and access to prompt diagnosis and treatment are still challenging issues in some Asian regions. The former represents a significant obstacle limiting the access of patients to MPA despite the proven efficacy of the drug as an induction agent and its superiority over azathioprine (AZA) in preventing disease flares when used for long-term maintenance immunosuppression. Calcineurin inhibitors such as tacrolimus deserve further investigation in view of their additional effect on podocytes by reducing proteinuria and the promising data from Asian patients. Despite considerable advances in the clinical management of LN over the past few decades with resultant improvements in patients' outcomes, there are still knowledge gaps and unmet clinical needs. Asia has made substantial contributions to the evidence base that guides clinical management and continues to offer invaluable opportunities for research pursuits. Key Messages: Treatment responses and clinical outcomes in Asian patients with LN compare favorably with patients from other parts of the world. The prevention and treatment of infective complications remain significant challenges in managing LN in Asia. Facts from East and West: (1) The prevalence of SLE is lower among Caucasians than other ethnicities. A higher prevalence is observed among Asians and African Americans, while the highest prevalence is found in Caribbean people. The prevalence of LN in Asian SLE patients is much higher than in Caucasians as well. However, the 10-year renal outcome and renal survival rate appear to be better in Asians. (2) Polymorphisms of genes involved in the immune response, such as Fcγ receptor, integrin alpha M, TNF superfamily 4, myotubularin-related protein 3 and many others, might be partly responsible for the differences in prevalence between the different ethnic groups. European ancestry was shown to be associated with a decrease in the risk of LN even after adjustment for genes most associated with renal disease. (3) Access...

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Pharmacokinetics of mycophenolic acid in severe lupus nephritis

Cited by 73 publications

References 32 publications

Exposure–effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis

Exposure–effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis

Mycophenolate as Induction Therapy in Lupus Nephritis with Renal Function Impairment

Lupus Nephritis in Asia: Clinical Features and Management

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