Legemiddelinteraksjoner og immunsuppresjon hos organtransplanterte

Vethe, Nils Tore; Midtvedt, Karsten; Åsberg, Anders; Amundsen, Rune; Bergan, Stein

doi:10.4045/tidsskr.11.0138

Cited by 7 publications

(1 citation statement)

References 49 publications

(60 reference statements)

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“…Indeed, in situations with coexistent illnesses, PXR activation can adversely affect (i.e., inactivate) other concomitantly delivered drugs, including anti-HIV (human immunodeficiency virus) protease inhibitors, oral contraceptive, thiazolidinediones, and benzodiazepines, such as midazolam and methadone (CYP3A substrates) (Biswas et al, 2009; Niemi et al, 2003; Back and Orme, 1990; Barry et al, 1997; Dowell et al, 2004; Grub et al, 2001; Jayasagar et al, 2003; Kakuda et al, 2011; Lotsch et al, 2002; Meyer, 1976; Pea et al, 2008; Poirer et al, 2007; Rosskopf et al, 2009; Schafer-Korting, 1993; Sheen, 2007; Vethe et al, 2011). Clinical consequences of such adverse interactions are observed with cyclosporine (transplant rejection) (Ruschitzka et al, 2000), loss of drug efficacy (anti-HIV and coadministered drugs) (Curran and Ribera, 2011; Kredo et al, 2011), potential loss of efficacy of irinotecan, despite added benefit of protection from intestinal toxicity when PXR is activated (Borrelli and Izzo, 2009; Hu et al, 2007), loss of efficacy with imatinib (approved treatment for chronic myeloid leukemia) (Borrelli and Izzo, 2009), methadone withdrawal (Kharasch et al, 2005; Bending and Skacel, 1977; Fromm et al, 1997; Holmes, 1990; Kreek et al, 1976; Anonymous, 2006), and fatigue with selective serotonin reuptake inhibitors (Hu et al, 2007; Cheng et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

PXR antagonists and implication in drug metabolism

Mani

Dou

Redinbo

2013

Drug Metabolism Reviews

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Adopted orphan nuclear receptor (NR), pregnane X receptor (PXR), plays a central role in the regulation of xeno- and endobiotic metabolism. Since the discovery of the functional role of PXR in 1998, there is evolving evidence for the role of PXR agonists in abrogating metabolic pathophysiology (e.g., cholestasis, hypercholesterolemia, and inflammation). However, more recently, it is clear that PXR is also an important mediator of adverse xeno- (e.g., enhances acetaminophen toxicity) and endobiotic (e.g., hepatic steatosis) metabolic phenotypes. Moreover, in cancer therapeutics, PXR activation can induce drug resistance, and there is growing evidence for tissue-specific enhancement of the malignant phenotype. Thus, in these instances, there may be a role for PXR antagonists. However, as opposed to the discovery efforts for PXR agonists, there are only a few antagonists described. The mode of action of these antagonists (e.g., sulforaphane) remains less clear. Our laboratory efforts have focused on this question. Since the original discovery of azoles analogs as PXR antagonists, we have preliminarily defined an important PXR antagonist pharmacophore and developed less-toxic PXR antagonists. In this review, we describe our published and unpublished findings on recent structure-function studies involving the azole chemical scaffold. Further work in the future is needed to fully define potent, more-selective PXR antagonists that may be useful in clinical application.

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Section: Introductionmentioning

confidence: 99%

PXR antagonists and implication in drug metabolism

Mani

Dou

Redinbo

2013

Drug Metabolism Reviews

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Immunosuppression in pediatric liver transplant recipients: Unique aspects

et al. 2017

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Pediatric liver transplantation has experienced improved outcomes over the last 50 years. This can be attributed in part to establishing optimal use of immunosuppressive agents to achieve a balance between minimizing the risks of allograft rejection and infection. The management of immunosuppression in children is generally more complex and can be challenging when compared with the use of these agents in adult liver transplant patients. Physiologic differences in children alter the pharmacokinetics of immunosuppressive agents, which affects absorption, distribution, metabolism, and drug excretion. Children also have a longer expected period of exposure to immunosuppression, which can impact growth, risk of infection (bacterial, viral, and fungal), carcinogenesis, and likelihood of nonadherence. This review discusses immunosuppressive options for pediatric liver transplant recipients and the unique issues that must be addressed when managing this population. Further advances in the field of tolerance and accommodation are needed to relieve the acute and cumulative burden of chronic immunosuppression in children.Liver Transplantation 23 244-256 2017 AASLD.

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Induction and Standard Immunosuppression

Newland¹,

Nemeth²

2018

Solid Organ Transplantation in Infants and Children

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Legemiddelinteraksjoner og immunsuppresjon hos organtransplanterte

Cited by 7 publications

References 49 publications

PXR antagonists and implication in drug metabolism

PXR antagonists and implication in drug metabolism

Immunosuppression in pediatric liver transplant recipients: Unique aspects

Induction and Standard Immunosuppression

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