Therapeutic drug monitoring of mycophenolic acid in patients with psoriasis

Daudén, E.; Pedraz, J.; Álvarez-Ruiz, Sara; García-Río, Irene; Sánchez-Peinado, Carmen; Oñate, María-Jesús; García‐Diez, Amaro

doi:10.1684/ejd.2010.0899

Cited by 4 publications

(2 citation statements)

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“…MMF decreases the recruitment of lymphocytes and monocytes, and consequently reduces the production of TNF-α and IL-1β into inflammatory sites in vivo [ 15 , 16 , 17 ]. Furthermore, a growing number of clinical reports showed the efficacy of this drug in the suppression of chronic inflammatory disorders and autoimmune disease, such as rheumatoid arthritis [ 15 ], pemphigus vulgaris [ 16 ], and psoriasis [ 18 ]. The use of MMF in IBD patients especially in those who are steroid-dependent, refractory, or intolerant of more conventional therapies has been documented.…”

Section: Introductionmentioning

confidence: 99%

Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn’s Disease Mouse Model

Liu

et al. 2015

IJMS

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Mycophenolate mofetil (MMF) is an alternative immunosuppressive agent that has been reported to be effective and well tolerated for the treatment of refractory inflammatory bowel disease (IBD). The aim of this study was to investigate the therapeutic effect of MMF on intestinal injury and tissue inflammation, which were caused by Crohn’s disease (CD). Here, trinitrobenzene sulfonic acid-relapsing (TNBS) colitis was induced in mice; then, we measured the differentiation of Th1/Th2 cells in mouse splenocytes by flow cytometry and the secretion of cytokines in mice with TNBS-induced colitis by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay (RT-PCR/ELISA). The results show that MMF significantly inhibited mRNA expression of pro-inflammatory cytokines IFN-γ, TNF-α, IL-12, IL-6, and IL-1β in mice with TNBS-induced colitis; however, MMF did not inhibit the expression of IL-10 mRNA. Additionally, ELISA showed that the serum levels of IFN-γ, TNF-α, IL-12, IL-6, and IL-1β were down-regulated in a TNBS model of colitis. Flow cytometric analysis showed MMF markedly reduced the percentages of Th1 and Th2 splenocytes in the CD mouse model. Mycophenolic acid (MPA) also significantly decreased the percentages of splenic Th1 and Th2 cells in vitro. Furthermore, MMF treatment not only significantly ameliorated diarrhea, and loss of body weight but also abrogated the histopathologic severity and inflammatory response of inflammatory colitis, and increased the survival rate of TNBS-induced colitic mice. These results suggest that treatment with MMF may improve experimental colitis and induce inflammatory response remission of CD by down-regulation of pro-inflammatory cytokines via modulation of the differentiation of Th1/Th2 cells.

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Section: Introductionmentioning

confidence: 99%

Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn’s Disease Mouse Model

Liu

et al. 2015

IJMS

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“…On one hand, some studies show that Psoriasis Area and Severity Index scores, and psoriasis improvement in general, do not correlate with MPA levels. 12,13 On the other hand, prospective studies of systemic lupus erythematosus show that the individual variability in response is related to differences in individual pharmacokinetics and not to the dose of MMF. 14 They report a relationship between MPA exposure and immunologic disease activity markers.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic dose monitoring of mycophenolate mofetil in dermatologic diseases

Sokumbi

el-Azhary

Langman

2013

Journal of the American Academy of Dermatology

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Clinical Pharmacokinetics and Pharmacodynamics of Mycophenolate in Patients with Autoimmune Disease

2013

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Mycophenolic acid (MPA), the active drug moiety of mycophenolate, is a potent immunosuppressant agent, which is increasingly being used in the treatment of patients with various autoimmune diseases. An understanding of the pharmacokinetics and pharmacodynamics of mycophenolate in this population should assist the clinician with rational dosage decisions. This review aims to provide an overview of the published literature on the clinical pharmacokinetics of mycophenolate in autoimmune disease and a briefer summary of current pharmacodynamic knowledge, and to identify areas of potential future research in this field. A literature search was conducted using PubMed and EMBASE databases as well as bibliographies of relevant articles and 'on-line early' pages of key journals. Twenty-six pharmacokinetic/pharmacodynamic studies of mycophenolate in people with autoimmune disease were identified and appraised. Twenty-two of these studies used non-compartmental analysis techniques and four used population modelling methods to estimate mycophenolate pharmacokinetic parameters. Seven studies linked mycophenolate exposure to treatment outcomes. Only four studies measured free (unbound) as well as total mycophenolate exposure and only two studies characterised MPA disposition following enteric-coated mycophenolate sodium (EC-MPS) administration. Across all studies MPA displayed erratic and complex pharmacokinetics with substantial between-subject variability. Based on total drug measurement, the dose-normalised MPA area under the plasma concentration-time curve (AUC) from 0 to 12 h post-dose (AUC12) varied at least five- to ten-fold between subjects. Typical values for apparent oral clearance (CL/F) of MPA during nonlinear mixed-effects modelling ranged from 8.3 to 25.3 L/h. Patient renal function, serum albumin levels, sex, ethnicity, food intake, concurrent administration of interacting drugs such as antacids, metal-containing medications and proton pump inhibitors and polymorphisms in genes encoding uridine diphosphate glucuronosyltransferase were identified in some studies as having a significant influence on the pharmacokinetics of mycophenolate. Typical MPA CL/F values in autoimmune disease patients were generally slightly lower than values published previously in population pharmacokinetic studies involving renal allograft recipients, possibly because of usage of ciclosporin, poorer renal function or lower serum albumin levels in the renal transplant cohort. In a single crossover study involving ten subjects only, significantly higher MPA AUC12 and maximum MPA concentration (C max) and lower MPA CL/F were reported following EC-MPS administration compared to mycophenolate mofetil administration. MPA exposure correlated well with treatment efficacy in patients with autoimmune disease (response to treatment, active disease and disease markers); however the relationship between MPA exposure and adverse events (infectious episodes, haematological toxicity and gastrointestinal symptoms) was unclear. Further investigation is re...

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Therapeutic drug monitoring of mycophenolic acid in patients with psoriasis

Cited by 4 publications

References 0 publications

Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn’s Disease Mouse Model

Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn’s Disease Mouse Model

Therapeutic dose monitoring of mycophenolate mofetil in dermatologic diseases

Clinical Pharmacokinetics and Pharmacodynamics of Mycophenolate in Patients with Autoimmune Disease

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