Safety and anti-HCV effect of prolonged intravenous silibinin in HCV genotype 1 subjects in the immediate liver transplant period

Bárcena, Rafael; Moreno, Ana; Rodríguez-Gandía, Miguel Ángel; Albillos, Agustı́n; Arocena, C; Blesa, C.; García-Hoz, F; Graus, Javier; Nuño, Javier; López-Hervás, P; Gajate, Luis; Martínez, A.; Bermejo, Teresa de Jesús; Mateos, María Luisa; Campo, Santos del

doi:10.1016/j.jhep.2012.10.009

Cited by 29 publications

(32 citation statements)

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“…However, silibinin's solubility profile remains a hurdle, making intravenous infusion of the chemically modified silibinin the only currently recommended route for clinical administration against HCV 12–14 18 19. This issue likely contributed to the lack of sufficient anti-HCV efficacy in a recent clinical trial of oral silymarin against chronic hepatitis C, despite the high dose (420–700 mg, 3× daily) used in the study 31.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, independent case reports suggest that intravenous silibinin could help prevent graft reinfection,15 16 prompting clinical trials for its use in the liver transplant setting of hepatitis C 17. Specifically, long-term intravenous silibinin treatment in many different cohorts displays robust anti-HCV activity without significant toxicity 14 18 19. These outcomes have resulted in silibinin acquiring an orphan drug designation (EU/3/10/828) from the European Medicines Agency for the prevention of recurrent hepatitis C in liver transplant patients as of 2010 20.…”

Section: Introductionmentioning

confidence: 99%

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Highly bioavailable silibinin nanoparticles inhibit HCV infection

Liu

Lin

Hsu

et al. 2016

Gut

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Highly bioavailable silibinin nanoparticles inhibit HCV infection

Liu

Lin

Hsu

et al. 2016

Gut

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“…Presently, there are no reports on signs of severe toxicity induced by Silibinin, but transient hyperbilirubinemia and mild sensation of heat with infusion were found as the most relevant drug-associated side effects [61, 62]. Combined with our study, although Silibinin was regarded as a promising drug candidate with a lower toxicity in existing researches, it should be highlighted with the adverse event on hemopathy in progressive clinical surveillances, especially for the old and infants or people with weak metabolism abilities.…”

Section: Resultsmentioning

confidence: 99%

Predicting the Drug Safety for Traditional Chinese Medicine through a Comparative Analysis of Withdrawn Drugs Using Pharmacological Network

Xue

Zhang

Cai

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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As the major issue to limit the use of drugs, drug safety leads to the attrition or failure in clinical trials of drugs. Therefore, it would be more efficient to minimize therapeutic risks if it could be predicted before large-scale clinical trials. Here, we integrated a network topology analysis with cheminformatics measurements on drug information from the DrugBank database to detect the discrepancies between approved drugs and withdrawn drugs and give drug safety indications. Thus, 47 approved drugs were unfolded with higher similarity measurements to withdrawn ones by the same target and confirmed to be already withdrawn or discontinued in certain countries or regions in subsequent investigations. Accordingly, with the 2D chemical fingerprint similarity calculation as a medium, the method was applied to predict pharmacovigilance for natural products from an in-house traditional Chinese medicine (TCM) database. Among them, Silibinin was highlighted for the high similarity to the withdrawn drug Plicamycin although it was regarded as a promising drug candidate with a lower toxicity in existing reports. In summary, the network approach integrated with cheminformatics could provide drug safety indications effectively, especially for compounds with unknown targets or mechanisms like natural products. It would be helpful for drug safety surveillance in all phases of drug development.

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“…Although high-dose oral silybin-phytosome achieved high blood concentrations transiently, i.e., 1 h after the first silybin-phytosome dose silibinin blood levels reached a mean value of 19.7 microM, low levels of silibinin and no significant anti-tumor activity were seen in prostate cancer tissue [50]. By intravenous administration, doses of 20 mg/kg/day of silibinin monotherapy leads to safe, potent and time-dependent in vivo anti-viral effects in difficult-to-treat HIV/HCV-coinfected patients [51, 52]. Because repeated intravenous boluses may be problematic for some patients, the results observed strongly suggest that the oral use of a Eurosil 85 ® -based nutraceutical [53] could be the first silibinin formulation that represents “ exciting seeds of change for the prevention and treatment of cancer ” [8].…”

Section: Discussionmentioning

confidence: 99%

Response of brain metastasis from lung cancer patients to an oral nutraceutical product containing silibinin

et al. 2016

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Despite multimodal treatment approaches, the prognosis of brain metastases (BM) from non-small cell lung cancer (NSCLC) remains poor. Untreated patients with BM have a median survival of about 1 month, with almost all patients dying from neurological causes. We herein present the first report describing the response of BM from NSCLC patients to an oral nutraceutical product containing silibinin, a flavonoid extracted from the seeds of the milk thistle. We present evidence of how the use of the silibinin-based nutraceutical Legasil® resulted in significant clinical and radiological improvement of BM from NSCLC patients with poor performance status that progressed after whole brain radiotherapy and chemotherapy. The suppressive effects of silibinin on progressive BM, which involved a marked reduction of the peritumoral brain edema, occurred without affecting the primary lung tumor outgrowth in NSCLC patients. Because BM patients have an impaired survival prognosis and are in need for an immediate tumor control, the combination of brain radiotherapy with silibinin-based nutraceuticals might not only alleviate BM edema but also prove local control and time for either classical chemotherapeutics with immunostimulatory effects or new immunotherapeutic agents such as checkpoint blockers to reveal their full therapeutic potential in NSCLC BM patients. New studies aimed to illuminate the mechanistic aspects underlying the regulatory effects of silibinin on the cellular and molecular pathobiology of BM might expedite the entry of new formulations of silibinin into clinical testing for progressive BM from lung cancer patients.

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Safety and anti-HCV effect of prolonged intravenous silibinin in HCV genotype 1 subjects in the immediate liver transplant period

Cited by 29 publications

References 40 publications

Highly bioavailable silibinin nanoparticles inhibit HCV infection

Highly bioavailable silibinin nanoparticles inhibit HCV infection

Predicting the Drug Safety for Traditional Chinese Medicine through a Comparative Analysis of Withdrawn Drugs Using Pharmacological Network

Response of brain metastasis from lung cancer patients to an oral nutraceutical product containing silibinin

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