Mammalian Target of Rapamycin Inhibitor Monotherapy: Efficacy in Renal Transplantation

Franco, Antônio; Más-Serrano, Patricio; Contreras, Javier Pérez; Jiménez, L.; Rodríguez, David; Olivares, José

doi:10.1016/j.transproceed.2015.09.006

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…In some studies in transplant patients, rapamycin (sirolimus) and everolimus did not increase the risk of diabetes [90–96]. In one study, no patient, out of 21 patients treated with rapamycin, developed diabetes, while the incidence of diabetes was 7% in patients treated with either cyclosporine or tacrolimus [96].…”

Section: Metabolic Effects or Rapamycin And Starvationmentioning

confidence: 99%

Rapamycin for longevity: opinion article

Blagosklonny

2019

Aging

147

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From the dawn of civilization, humanity has dreamed of immortality. So why didn’t the discovery of the anti-aging properties of mTOR inhibitors change the world forever? I will discuss several reasons, including fear of the actual and fictional side effects of rapamycin, everolimus and other clinically-approved drugs, arguing that no real side effects preclude their use as anti-aging drugs today. Furthermore, the alternative to the reversible (and avoidable) side effects of rapamycin/everolimus are the irreversible (and inevitable) effects of aging: cancer, stroke, infarction, blindness and premature death. I will also discuss why it is more dangerous not to use anti-aging drugs than to use them and how rapamycin-based drug combinations have already been implemented for potential life extension in humans. If you read this article from the very beginning to its end, you may realize that the time is now.

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Section: Metabolic Effects or Rapamycin And Starvationmentioning

confidence: 99%

Rapamycin for longevity: opinion article

Blagosklonny

2019

Aging

147

View full text Add to dashboard Cite

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“…[18,19] EVR in combination with MMF has shown promising renal outcomes after liver, heart, and kidney transplantation. [20–22] Moreover, mTOR inhibitors have been shown to prevent tumors and even to reduce metastatic tumor growth by angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Influence of cyclosporine and everolimus on the main mycophenolate mofetil pharmacokinetic parameters

et al. 2017

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The objective of the present study was to assess the effect of cyclosporine (CsA) on the pharmacokinetic parameters of mycophenolic acid (MPA), an active mycophenolate mofetil (MMF) metabolite, and to compare with the effect of everolimus (EVR).Anonymized medical records of 404 kidney recipients were reviewed. The main MPA pharmacokinetic parameters (AUC(0–12) and Cmax) were evaluated.The patients treated with a higher mean dose of CsA displayed higher MPA AUC(0–12) exposure in the low-dose MMF group (1000 mg/day) (40.50 ± 10.97 vs 28.08 ± 11.03 h mg/L; rs = 0.497, P < 0.05), medium-dose MMF group (2000 mg/day) (43.00 ± 6.27 vs 28.85 ± 11.08 h mg/L; rs = 0.437, P < 0.01), and high-dose MMF group (3000 mg/day) (56.75 ± 16.78 vs 36.20 ± 3.70 h mg/L; rs = 0.608, P < 0.05).A positive correlation was also observed between the mean CsA dose and the MPA Cmax in the low-dose MMF group (Cmax 22.83 ± 10.82 vs 12.08 ± 5.59 mg/L; rs = 0.507, P < 0.05) and in the medium-dose MMF group (22.77 ± 8.86 vs 13.00 ± 6.82 mg/L; rs = 0.414, P < 0.01).The comparative analysis between 2 treatment arms (MMF + CsA and MMF + EVR) showed that MPA AUC(0–12) exposure was by 43% higher in the patients treated with a medium dose of MMF and EVR than in the patients treated with a medium dose of MMF and CsA.The data of the present study suggest a possible CsA versus EVR influence on MMF pharmacokinetics. Study results show that CsA has an impact on the main MPA pharmacokinetic parameters (AUC(0–12) and Cmax) in a CsA dose-related manner, while EVR mildly influence or does not affect MPA pharmacokinetic parameters. Low-dose CsA (lower than 180 mg/day) reduces MPA AUC(0–12) exposure under the therapeutic window and may lead to ineffective therapy, while a high-dose CsA (>240 mg/day) is related to greater than 10 mg/L MPA Cmax and increases the likelihood of adverse events.

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