Temporal shifts in safety and efficacy profile of mycophenolate mofetil 2 g versus 3 g daily early after heart transplantation

Braghieri, Lorenzo; Jennings, Douglas L.; Bohn, Bruno; Habal, Marlena V.; Pinsino, A.; Mondellini, G.M.; Ladanyi, Annamaria; Latif, F.; Clerkin, Kevin J.; Restaino, Susan; Kurlansky, Paul; Takeda, Koji; Naka, Yoshifumi; Demmer, Ryan T.; Sayer, Gabriel; Uriel, Nir; Colombo, P.C.; Yuzefpolskaya, M.

doi:10.1002/phar.2724

Cited by 2 publications

(12 citation statements)

References 28 publications

(61 reference statements)

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“…After excluding the publications not complying with inclusion criteria, 86 records were considered suitable for full-text analysis. After reading these papers and examining their content the two reviewers identified 50 papers [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ,…”

Section: Resultsmentioning

confidence: 99%

“…Nineteen papers were investigations performed only in humans. Eighteen of them were observational studies [ 21 , 22 , 24 , 27 , 28 , 29 , 32 , 33 , 35 , 38 , 40 , 41 , 54 , 55 , 56 , 60 , 64 , 65 ] and only one was a randomized clinical trial [ 59 ].…”

Section: Resultsmentioning

confidence: 99%

“…We found no studies on the effect of the intestinal microbiota on EVERO or SIR. Seventeen studies showed significant effect of fecal microbiota, or enzymes produced by intestinal bacteria on cIMDs [ 21 , 22 , 23 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 38 , 39 , 40 ], whereas no effect was observed in the remaining three studies [ 24 , 36 , 37 ].…”

Section: Resultsmentioning

confidence: 99%

“…Seven papers reported results of studies performed in vitro either by using living cells (cell lines or bacteria) or acellular systems with cell extracts or purified enzymes [ 23 , 25 , 26 , 30 , 31 , 36 , 37 ], twelve papers were on studies performed in vivo [ 21 , 22 , 24 , 27 , 28 , 29 , 32 , 34 , 35 , 38 , 39 , 40 ] and one included both in vitro ed in vivo experiments [ 33 ]. Seven of the in vitro studies evaluated cIMD metabolism either by cultured fecal bacteria from human stool (two papers [ 25 , 26 ]), or by human fecal material (three papers [ 33 , 36 , 37 ]) or by purified enzymes (two papers [ 30 , 31 ]).…”

Section: Resultsmentioning

confidence: 99%

“…The main findings of the selected studies were summarized in a narrative form in the text of the article and in two tables, the first ( Table 1 ) concerning the papers on the effect of the intestinal microbiota on cIMDs [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ], and the second ( Table 2 ) concerning the papers on effect of cIMDs on intestinal microbiota [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ,…”

Section: Methodsmentioning

confidence: 99%

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Pharmacomicrobiomics of Classical Immunosuppressant Drugs: A Systematic Review

Manes,

Di Renzo,

Dodani

et al. 2023

Biomedicines

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The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Pharmacomicrobiomics of Classical Immunosuppressant Drugs: A Systematic Review

Manes,

Di Renzo,

Dodani

et al. 2023

Biomedicines

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Pharmacomicrobiomics: Immunosuppressive Drugs and Microbiome Interactions in Transplantation

Mohamed,

Saqr,

Staley

et al. 2024

Transplantation

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The human microbiome is associated with human health and disease. Exogenous compounds, including pharmaceutical products, are also known to be affected by the microbiome, and this discovery has led to the field of pharmacomicobiomics. The microbiome can also alter drug pharmacokinetics and pharmacodynamics, possibly resulting in side effects, toxicities, and unanticipated disease response. Microbiome-mediated effects are referred to as drug–microbiome interactions (DMI). Rapid advances in the field of pharmacomicrobiomics have been driven by the availability of efficient bacterial genome sequencing methods and new computational and bioinformatics tools. The success of fecal microbiota transplantation for recurrent Clostridioides difficile has fueled enthusiasm and research in the field. This review focuses on the pharmacomicrobiome in transplantation. Alterations in the microbiome in transplant recipients are well documented, largely because of prophylactic antibiotic use, and the potential for DMI is high. There is evidence that the gut microbiome may alter the pharmacokinetic disposition of tacrolimus and result in microbiome-specific tacrolimus metabolites. The gut microbiome also impacts the enterohepatic recirculation of mycophenolate, resulting in substantial changes in pharmacokinetic disposition and systemic exposure. The mechanisms of these DMI and the specific bacteria or communities of bacteria are under investigation. There are little or no human DMI data for cyclosporine A, corticosteroids, and sirolimus. The available evidence in transplantation is limited and driven by small studies of heterogeneous designs. Larger clinical studies are needed, but the potential for future clinical application of the pharmacomicrobiome in avoiding poor outcomes is high.

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Temporal shifts in safety and efficacy profile of mycophenolate mofetil 2 g versus 3 g daily early after heart transplantation

Cited by 2 publications

References 28 publications

Pharmacomicrobiomics of Classical Immunosuppressant Drugs: A Systematic Review

Pharmacomicrobiomics of Classical Immunosuppressant Drugs: A Systematic Review

Pharmacomicrobiomics: Immunosuppressive Drugs and Microbiome Interactions in Transplantation

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