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MMF and polymorphism

Kazuaki Yoshimura, Ikuko Yano, Takashi Yamamoto, Tadakazu Kondo, Misaki Kawanishi, Yui Isomoto, Atsushi Yonezawa, Akifumi Takaori-Kondo, Kazuo Matsubara
Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) and is frequently used to prevent acute graft-versus-host disease (aGVHD) in patients receiving hematopoietic stem cell transplantation (HSCT). However, optimal doses of MMF and target MPA concentrations in HSCT patients have not been defined. In this study, relationships between pharmacokinetic or pharmacodynamic markers of MPA and successful aGVHD prevention and neutrophil engraftment were evaluated to inform individualized MPA treatments in HSCT patients...
February 7, 2018: Biology of Blood and Marrow Transplantation
Zi-Cheng Yu, Pei-Jun Zhou, Xiang-Hui Wang, Bressolle Françoise, Da Xu, Wei-Xia Zhang, Bing Chen
Mycophenolate mofetil (MMF) is an important immunosuppressant used in renal transplantation, and mycophenolic acid (MPA) is the active component released from the ester prodrug MMF. The objective of this study was to investigate the population pharmacokinetics of mycophenolic acid (MPA) following oral administration of MMF in Chinese adult renal transplant recipients and to identify factors that explain MPA pharmacokinetic variability. Pharmacokinetic data for MPA and covariate information were retrospectively collected from 118 patients (79 patients were assigned to the group for building the population pharmacokinetic model, while 39 patients were assigned to the validation group)...
November 2017: Acta Pharmacologica Sinica
L R Ruschel, V M Schmitt, A B Silva, C S A Oliveira, K Flach, D O d'Avila, F V Thiesen
Mycophenolate mofetil (MMF) is a prodrug active only after its hydrolysis to mycophenolic acid (MPA). The UGT1A9 enzyme is of special interest since it is the main enzyme involved in the glucuronidation of MPA. Single nucleotide polymorphisms (SNPs) in the UGT1A9 gene may be responsible for individual differences in the pharmacokinetics of MMF. Expression levels and the activity of UGT1A9 may depend on the presence of some SNPs located in the gene promoter region (-2152C>T and -275T>A), as well as changes in the coding region (c...
May 31, 2017: Genetics and Molecular Research: GMR
H S Ciftci, M S Karadeniz, T Tefik, Y Caliskan, H Yazıcı, E Demir, A Turkmen, I Nane, F S Oguz, F Aydin
BACKGROUND: Most patients have serious digestive complications after renal transplantation. Therefore, it is important to protect gastrointestinal function to improve the survival rate of transplant patients. Proton pump inhibitors (PPIs) such as lansoprazole and rabeprazole are widely administered to renal transplant patients with mycophenolic acid (MPA) in the perioperative period. PPIs are metabolized by cytochrome (CYP) 2C19 enzymes. Mycophenolate sodium (MYF) and mycophenolate mofetil (MMF) have been used in immunosuppression...
April 2017: Transplantation Proceedings
Hideaki Kagaya, Takenori Niioka, Mitsuru Saito, Takamitsu Inoue, Kazuyuki Numakura, Tomonori Habuchi, Shigeru Satoh, Masatomo Miura
1. The objective of this study was to examine the association of UGT1A9, SLCO, and ABCC polymorphisms with mycophenolic acid (MPA) pharmacokinetics in ABO blood type (ABO) incompatible patients with severe renal dysfunction pre-transplantation. 2. In all patients, on day 14 after beginning mycophenolate mofetil (MMF) treatment (1 week before transplantation) and on day 28 after renal transplantation, samples were collected just prior to and 1, 2, 3, 4, 6, 9, and 12 h after oral MMF administration. 3. The median dose-adjusted AUC0-12 of MPA after renal transplantation was significantly lower than before transplantation (57...
October 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Vladimir Tesar, Zdenka Hruskova
BACKGROUND: Lupus nephritis (LN) is still associated with significant mortality and substantial risk of progression to end-stage renal failure. Its outcome is related to the class and severity of LN and response to treatment, and it is poorer in patients with renal relapses. Ethnicity has a relatively well-defined impact on the outcome of the patients and their response to treatment and must always be taken into consideration in treatment decisions. SUMMARY: In this article, we provide a review of the impact of ethnicity on the prevalence of systemic lupus erythematosus (SLE), the proportion of patients with SLE developing LN, outcomes of SLE and LN and response of LN to treatment...
September 2015: Kidney Diseases
Desmond Y H Yap, Tak Mao Chan
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...
September 2015: Kidney Diseases
Chalermrat Bunchorntavakul, K Rajender Reddy
Management of hepatitis C (HCV) in liver transplantation (LT) population presents unique challenges. Suboptimal graft survival in HCV+ LT recipients is attributable to universal HCV recurrence following LT. Although eradication of HCV prior to LT is ideal for the prevention of HCV recurrence it is often limited by adverse events, particularly in patients with advanced cirrhosis. Antiviral therapy in LT candidates needs careful monitoring, and prophylaxis with HCV antibodies is ineffective. Early antiviral therapy after LT has been investigated, but no clear benefit has been demonstrated...
June 2014: Journal of Clinical and Translational Hepatology
Tomomi Kogiso, Katsutoshi Tokushige, Etsuko Hashimoto, Makiko Taniai, Akiko Omori, Yoshihito Kotera, Hiroto Egawa, Masakazu Yamamoto, Keiko Shiratori
Aim: Pegylated-interferon/ribavirin/simeprevir (PEG-IFN/RBV/SMV) combination therapy is widely used for hepatitis C virus (HCV) treatment after liver transplantation (LT). Here, we observed two cases of extended severe anemia during PEG-IFN/RBV/SMV therapy for HCV serological type 1 re-infected after LT. Immunosuppressants consisted of tacrolimus and mycophenolate mofetil (MMF). Case 1 was a 65-year-old-woman treated with PEG-IFN/RBV/SMV therapy and 500 mg MMF/day 9 months after LT. Her serum hemoglobin (Hb) level decreased from 10 to 8...
June 2015: Clinical Journal of Gastroenterology
Julie G Ledford, Dennis R Voelker, Kenneth J Addison, Ying Wang, Vinayak S Nikam, Simone Degan, Pitachaimani Kandasamy, Sasipa Tanyaratsrisakul, Bernard M Fischer, Monica Kraft, John W Hollingsworth
Mycoplasma pneumoniae is an extracellular pathogen that colonizes mucosal surfaces of the respiratory tract and is associated with asthma exacerbations. Previous reports demonstrate that surfactant protein-A (SP-A) binds live M. pneumoniae and mycoplasma membrane fractions (MMF) with high affinity. Humans express a repertoire of single-amino acid genetic variants of SP-A that may be associated with lung disease, and our findings demonstrate that allelic differences in SP-A2 (Gln223Lys) affect the binding to MMF...
June 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Xiao-chun Xie, Jun Li, Hong-yang Wang, Hong-liang Li, Jing Liu, Qian Fu, Jia-wen Huang, Chen Zhu, Guo-ping Zhong, Xue-ding Wang, Ping-ping Sun, Min Huang, Chang-xi Wang, Jia-li Li
AIM: To evaluate the effects of UDP-glucuronosyltransferases (UGTs) polymorphisms on the pharmacokinetics of the immunosuppressant mycophenolate mofetil (MMF) in Chinese renal transplant recipients. METHODS: A total of 127 renal transplant patients receiving MMF were genotyped for polymorphisms in UGT1A9 -1818T>C, I399C>T, -118T9/10, -440C>T, -331T>C, UGT2B7 IVS1+985A>G, 211G>T, -900A>G, UGT1A8 518C>G and UGT1A7 622T>C. The plasma concentrations of the MMF active moiety mycophenolic acid (MPA) and main metabolite 7-O-MPA-glucuronide (MPAG) were analyzed using HPLC...
May 2015: Acta Pharmacologica Sinica
Su Kang Kim, Hae Jeong Park, Hosik Seok, Hye Sook Jeon, Tae Won Lee, Sang Ho Lee, Ju Young Moon, Chun Gyoo Ihm, Tae Hee Kim, Yeong Hoon Kim, Sun Woo Kang, Seok Ju Park, Kyung Hwan Jeong, Joo-Ho Chung
Recent studies have shown that single-nucleotide polymorphisms (SNPs) are associated with allograft rejection in kidney transplantation recipients. We evaluated the possible association between SNPs of the cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1) gene, and acute rejection (AR) among renal transplant patients in a Korean population. We conducted a case-control association study in 63 AR and 284 non-AR kidney transplant recipients. The SNPs of CYP2E1 were genotyped by direct sequencing. Recipient sex (p = 0...
June 2014: Clinical Transplantation
H Krichen, Y Gorgi, T Dhaouadi, Y Mecheri, I Sfar, R Bardi, M M Bacha, E Abderrahim, S Jendoubi-Ayed, K Ayed, T Ben Abdallah
BACKGROUND: Acute and chronic rejections remain an important cause of graft loss after renal transplantation. Currently, activation of innate immune responses through Toll-like receptors (TLRs) is suspected to be implied in the loss of the transplant tolerance. OBJECTIVES: We investigated functional single nucleotide polymorphisms (SNPs) of TLR4 and its coreceptor CD14 in kidney transplantation and looked for any potential role in acute rejection (AR) and chronic allograft nephropathy (CAN) and impact on graft survival...
2013: Transplantation Proceedings
Talia Mazidi, Mohammad-Reza Rouini, Mohammad-Hossein Ghahremani, Simin Dashti-Khavidaki, Mahboob Lessan-Pezeshki, Farrokh Lagha Ahmadi, Jamshid Salam-Zadeh, Ali Mandegary, Kheirollah Gholami
There are wide individual differences in pharmacokinetic parameters of mycophenolate mofetil (MMF) among transplanted patients. Some studies have shown that single nucleotide polymorphisms (SNPs) of the Uridine Diphosphate Glucuronosyl Transferase1A9 (UGT1A9) are responsible for these differences in early days after transplantation. Therefore it was decided to evaluate the influence of UGT polymorphism on MMF pharmacokinetics among stable Iranian transplant patients. This was a cross sectional study from March 2008 through December 2008 in Imam Khomeini Hospital affiliated to the Tehran University of Medical Sciences in Iran...
2013: Iranian Journal of Pharmaceutical Research: IJPR
T Dhaouadi, I Sfar, R Bardi, S Jendoubi-Ayed, T B Abdallah, K Ayed, Y Gorgi
BACKGROUND: Acute and chronic rejections remain an important cause of graft loss after renal transplantation. It has been suggested that cytokine genotyping may have a predictive role to identify patients at greater risk of rejection regardless of human leukocyte antigen (HLA) compatibility and/or the presence of anti-HLA antibodies before the renal allograft. OBJECTIVES: We sought to investigate polymorphisms of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, interleukin (IL)-10, IL-6, and interferon (IFN)-γ as indices of differential cytokine production in kidney transplantation and to examine their predictive roles for acute or chronic rejection...
July 2013: Transplantation Proceedings
Valerie Said-Conti, Persis J Amrolia, Mark N Gaze, Sara Stoneham, Neil Sebire, Rukshana Shroff, Stephen D Marks
BACKGROUND: Primary central nervous system (PCNS) post-transplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation and is typically an Epstein-Barr virus (EBV)-induced B-cell CD20+ lymphoma. The modalities of treatment include reduction in immunosuppression, cranial radiotherapy (CRT), intravenous and intrathecal rituximab when CD20 is expressed on B-lymphocytes and PTLD cells, and chemotherapy. CASE-DIAGNOSIS/TREATMENT: We report the successful treatment of EBV-driven PCNS PTLD by reduction in immunosuppression (RI), CRT, and intravenous rituximab...
October 2013: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
J Pazik, M Ołdak, Z Lewandowski, M Podgórska, E Sitarek, R Płoski, Z Gałazka, A Kwiatkowski, J Malejczyk, M Durlik
BACKGROUND: Uridine diphosphate glucuronosyltransferase (UGT2B7) is responsible for conversion of mycophenolic acid to mycophenolic acyl-glucuronide (acylMPAG). Conflicting data exist regarding the role of UGT2B7 p.His268Tyr (802C>T, rs7439366) variant in the clinical course following organ transplantation. STUDY AIM: The aim of this study was to reveal an association between UGT2B7 p.His268Tyr (802C>T, rs7439366) polymorphism and kidney transplantation outcome...
May 2013: Transplantation Proceedings
Xiao-Ying Deng, Chang-Xi Wang, Xue-Ding Wang, Hui-Chang Bi, Xiao Chen, Jia-Li Li, Min Huang
Mycophenolate mofetil (MMF), a widely used immunosuppressant, is characterized by highly variable pharmacokinetics. UGT1A8, UGT1A9, UGT2B7 and ABCC2 have been proved to be critical genes associated with inter-individual variation of MMF pharmacokinetics. In this study, we investigated the genetic polymorphisms of UGT1A8*2, UGT1A8*3, UGT1A9 C-2152T, UGT1A9 T-275A, UGT1A9 T98C, UGT2B7*2, ABCC2 C-24T and ABCC2 C3972T in 200 Chinese renal transplant recipients and compared them with those in other ethnic groups reported in the literature, to start the exploration of a better use of MMF in Chinese...
April 2013: Die Pharmazie
Niloufar Mohammadpour, Sepideh Elyasi, Naser Vahdati, Amir Hooshang Mohammadpour, Jamal Shamsara
: Immunosuppressants require therapeutic drug monitoring because of their narrow therapeutic index and significant inter-individual variability in blood concentrations. This variability can be because of factors like drug-nutrient interactions, drug-disease interactions, renal-insufficiency, inflammation and infection, gender, age, polymorphism and liver mass. Drug monitoring is widely practiced especially for cyclosporine, tacrolimus, sirolimus and mycophenolic acid. CYCLOSPORINE: Therapeutic monitoring of immunosuppressive therapy with cyclosporine is a critical requirement because of intra- and inter-patient variability of drug absorption, narrow therapeutic window and drug induced nephrotoxicity...
November 2011: Iranian Journal of Basic Medical Sciences
Dong Guo, Liang-Fang Pang, Yang Han, Hong Yang, Guo Wang, Zhi-Rong Tan, Wei Zhang, Hong-Hao Zhou
PURPOSE: To explore the impact of UDP-glucuronosyltransferase polymorphisms (UGT1A9-118(dT) 9/10 , UGT1A9 CI399T, UGT1A9 C-440T and UGT2B7 G211T) on the pharmacokinetics of mycophenolic acid (MPA) in healthy Chinese volunteers. METHODS: We recruited ten healthy volunteers with no polymorphisms (control group), 11 homozygotes of mutants UGT1A9 CI399T and UGT1A9-118(dT) 9/10 , ten heterozygotes of UGT1A9 C440T and seven carriers of UGT2B7 211T from a total of 518 healthy Chinese volunteers...
April 2013: European Journal of Clinical Pharmacology
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