Plasma mycophenolic acid concentration and the clinical outcome after lung transplantation

Yagi, Hiroshi; Matsuda, Yasushi; Watanabe, Tatsuaki; Eba, Shunsuke; Hoshi, Fumihiko; Hirama, Takashi; Oishi, Hisashi; Sado, Tetsu; Noda, Masafumi; Sakurada, Akira; Kikuchi, Masafumi; Yamaguchi, Hiroaki; Mano, Nariyasu; Okada, Yoshinori

doi:10.1111/ctr.14088

Cited by 7 publications

(6 citation statements)

References 30 publications

(52 reference statements)

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“…Better results can be obtained with an additional measurement after 4 h (C 4 ) and utilization of the following formula: AUC 0–12 = 8.217 + 3.163 × C 0 + 0.994 × C 1 + 1.334 × C 2 + 4.183 × C 4 . According to Yakubi et al, the preferred AUC 0–12 range lies between 22.8 and 40.5 μg × h/ml.” 57 – 59 TDM of mycophenolate mofetil represents a clinical-pharmacological challenge to physicians and is considerably more complex than conventional TDM. Several measurements of mycophenolate plasma levels after drug intake as well as the application of a multivariate linear regression equation are required.…”

Section: Resultsmentioning

confidence: 99%

Clinical-pharmacological drug information center of Hannover Medical School: experiences and analysis from a tertiary care university hospital

Heck

Stichtenoth

Sabau

et al. 2022

Sci Rep

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Drug information centers (DICs) are institutions dedicated to provide objective, independent, and up-to-date information on drugs and their rational use. To overcome the lack of recent DIC reports from central Europe, we analyzed all queries (n = 594) submitted to the DIC run by the Institute for Clinical Pharmacology of Hannover Medical School between October 2018 and April 2022. Approximately one in three queries (31.1%; 185/594) was submitted by internists. 82.8% (492/594) of the queries were patient-specific, while the remaining 17.2% (102/594) were general queries. Adverse drug reactions (ADRs), indications/contraindications, and pharmacodynamic interactions (PDIs) represented the three most frequently addressed query categories, being involved in 44.8% (266/594), 43.3% (257/594), and 34.3% (204/594) of all queries, respectively (assignment of more than one category per query was possible). As compared to general queries, patient-specific queries were statistically significantly more often related to ADRs, PDIs, and pharmacokinetic interactions (PKIs) (ADRs: 35.3% vs. 46.7%, P = 0.034; PDIs: 14.7% vs. 38.4%, P < 0.001; PKIs: 20.6% vs. 31.5%, P = 0.028). To demonstrate the complexity of queries submitted to the clinical-pharmacological DIC, we present and comment on an illustrative selection of queries.

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Section: Resultsmentioning

confidence: 99%

Clinical-pharmacological drug information center of Hannover Medical School: experiences and analysis from a tertiary care university hospital

Heck

Stichtenoth

Sabau

et al. 2022

Sci Rep

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“…AUC analysis is not performed for mycophenolic acid, for which reason we cannot relate our results to the mycophenolic acid AUC. Yabuki et al found large variations in patients after solid organ transplantation [25]. In addition, they reported that the mycophenolic acid AUC showed only a weak correlation with MPA 0 or mycophenolate mofetil dosage [25,26].…”

Section: Discussionmentioning

confidence: 99%

“…Yabuki et al found large variations in patients after solid organ transplantation [25]. In addition, they reported that the mycophenolic acid AUC showed only a weak correlation with MPA 0 or mycophenolate mofetil dosage [25,26].…”

Section: Discussionmentioning

confidence: 99%

Influence of mycophenolate mofetil dosage and plasma levels on the occurrence of chronic lung allograft dysfunction in lung transplants: a retrospective cohort analysis

Steinack¹,

Saurer²,

Gautschi³

et al. 2022

Swiss Med Wkly

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INTRODUCTION: Development of chronic lung allograft dysfunction is a limiting factor for post-lung transplant survival. We evaluated whether the dose of the immunosuppressant mycophenolate mofetil or plasma concentrations of the active metabolite mycophenolic acid affect the development of chronic lung allograft dysfunction. METHODS:In this retrospective cohort study we recruited 71 patients with a lung transplant between 2010 and 2014 which survived the first year after transplantation up to 1 July 2021. An event-time-analytical Cox proportionalhazards regression model with time-varying-covariates (18,431 measurements for MPA, mycophenolate mofetil dosage, lymphocytes) was used to predict chronic lung allograft dysfunction, with adjustment for sociodemographic factors and lung function at baseline. RESULTS: 37 patients did not develop chronic lung allograft dysfunction (age 41.3 ± 15.6 years, baseline FEV1 95.5 ± 19.1% predicted) and 34 patients developed chronic lung allograft dysfunction (age 50.9 ± 13.3 years, baseline FEV1 102.2 ± 25.4% predicted). Mean mycophenolic acid did not differ significantly between the groups (2.8 ± 1.7 and 3.0 ± 2.3 mg/l; p = 0.724). In the first 4 posttransplant years the death rate was 25%. A total of 50% of the patients died by the ninth post-transplant year. There was a dose-effect relationship between mycophenolate mofetil dosage, mycophenolic acid (r 2 = 0.02, p <0.001), as well as lymphocyte levels (r 2 = -0.007, p <0.001), but only the traditional risk factor age predicted chronic lung allograft dysfunction. Continuously measured mycophenolic acid did not predict chronic lung allograft dysfunction (hazard ratio 0.98, 95% confidence interval 0.90-1.06, p = 0.64 over a period of 382.97 patient-years).CONCLUSION: Mycophenolate mofetil dosage and mycophenolic acid were not associated with chronic lung allograft dysfunction development. Thus, the mycophenolate mofetil dose or mycophenolic acid plasma concentration are not a primary factor related to organ rejection, but chronic lung allograft dysfunction may be influenced by other components of immunosuppression or other factors.

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“…Due to fluctuating plasma concentrations of MMF, area under the curve (AUC) was established as a relevant parameter for bioavailability and therapeutic drug monitoring. The ideal AUC has been reported to be 40-60 µg × h/mL (Ferreira et al, 2020) after renal transplantation and about 30-40 µg × h/mL after lung transplantation (Yabuki et al, 2020). However, it should be noted that the bioavailability in these studies was chosen to establish sufficient immunosuppression with few side effects.…”

Section: The Brain Cytoprotective Effect Of Mycophenolate Mofetil Dep...mentioning

confidence: 99%

Microglia-Dependent and Independent Brain Cytoprotective Effects of Mycophenolate Mofetil During Neuronal Damage

Kleine

Grabiec

Hohmann

et al. 2022

Front. Aging Neurosci.

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Acute lesions of the central nervous system often lead to permanent limiting deficits. In addition to the initial primary damage, accompanying neuroinflammation is responsible for progression of damage. Mycophenolate mofetil (MMF) as a selective inhibitor of inosine 5-monophosphate dehydrogenase (IMPDH) was shown to modulate the inflammatory response and promote neuronal survival when applied in specific time windows after neuronal injury. The application of brain cytoprotective therapeutics early after neuronal damage is a fundamental requirement for a successful immunomodulation approach. This study was designed to evaluate whether MMF can still mediate brain cytoprotection when applied in predefined short time intervals following CNS injury. Furthermore, the role of microglia and changes in IMPDH2 protein expression were assessed. Organotypic hippocampal slice cultures (OHSC) were used as an in vitro model and excitotoxically lesioned with N-methyl-aspartate (NMDA). Clodronate (Clo) was used to deplete microglia and analyze MMF mediated microglia independent effects. The temporal expression of IMPDH2 was studied in primary glial cell cultures treated with lipopolysaccharide (LPS). In excitotoxically lesioned OHSC a significant brain cytoprotective effect was observed between 8 and 36 h but not within 8 and 24 h after the NMDA damage. MMF mediated effects were mainly microglia dependent at 24, 36, 48 h after injury. However, further targets like astrocytes seem to be involved in protective effects 72 h post-injury. IMPDH2 expression was detected in primary microglia and astrocyte cell cultures. Our data indicate that MMF treatment in OHSC should still be started no later than 8–12 h after injury and should continue at least until 36 h post-injury. Microglia seem to be an essential mediator of the observed brain cytoprotective effects. However, a microglia-independent effect was also found, indicating involvement of astrocytes.

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Plasma mycophenolic acid concentration and the clinical outcome after lung transplantation

Cited by 7 publications

References 30 publications

Clinical-pharmacological drug information center of Hannover Medical School: experiences and analysis from a tertiary care university hospital

Clinical-pharmacological drug information center of Hannover Medical School: experiences and analysis from a tertiary care university hospital

Influence of mycophenolate mofetil dosage and plasma levels on the occurrence of chronic lung allograft dysfunction in lung transplants: a retrospective cohort analysis

Microglia-Dependent and Independent Brain Cytoprotective Effects of Mycophenolate Mofetil During Neuronal Damage

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