Pharmacokinetic Drug Interactions of Afatinib with Rifampicin and Ritonavir

Wind, Sven; Gießmann, Thomas; Jungnik, Arvid; Brand, Tobias; Marzin, Kristell; Bertulis, Julia; Hocke, Julia; Ganßer, Dietmar; Stopfer, Peter

doi:10.1007/s40261-013-0161-2

Cited by 55 publications

(49 citation statements)

References 21 publications

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“…Furthermore, it has been suggested that rifampicin activates P-gp in vivo and in vitro [11,12]. Although there are some other studies about the effects of P-glycoprotein modulation on the bioavailability of several drugs [16][17][18], to best of the authors' knowledge, this is the first study to investigate the effects of P-gp-inhibiting and -activating drugs on the intestinal absorption of immunosuppressive drugs.…”

Section: Discussionmentioning

confidence: 91%

The Effect of P-Glycoprotein Inhibition and Activation on the Absorption and Serum Levels of Cyclosporine and Tacrolimus in Rats

2016

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Section: Discussionmentioning

confidence: 91%

The Effect of P-Glycoprotein Inhibition and Activation on the Absorption and Serum Levels of Cyclosporine and Tacrolimus in Rats

2016

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“…Inhibitors of P-gp, such as ritonavir can increase concentrations of afatinib, while inducers of P-gp reduce afatinib levels. The clinical consequences of concurrent use of afatinib with P-gp inducers/inhibitors are questionable, and these drugs can be administered 6-12 hours apart to avoid significant interactions [85].…”

Section: Clinical Safetymentioning

confidence: 99%

Tyrosine kinase inhibitors for EGFR- and ALK-mutated non-small cell lung cancer

Thompson

Menon

2016

ADMET DMPK

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Discovery of the epidermal growth receptor (EGFR) activating mutations and anaplastic lymphoma kinase (ALK) rearrangements has expanded the therapeutic landscape in non-small cell lung cancer (NSCLC). Survival outcomes for patients with these mutations have improved dramatically with EGFR and ALK tyrosine kinase inhibitors (TKIs). Multiple generations of EGFR and ALK TKIs have been rapidly developed, and patients and clinicians now have several options for first-and second-line treatments. While these small molecule

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“…These preclinical data suggested the potential for afatinib to offer clinical benefit to patients with ErbB Family-driven tumours. Overall afatinib has a low potential for drug-drug interactions [67]. Afatinib is not metabolised but enzyme-catalysed metabolic reactions and is not an inhibitor or an inducer of the CYP enzymes [67].…”

Section: Afatinibmentioning

confidence: 99%

“…Overall afatinib has a low potential for drug-drug interactions [67]. Afatinib is not metabolised but enzyme-catalysed metabolic reactions and is not an inhibitor or an inducer of the CYP enzymes [67]. In vitro studies have shown that afatinib interacts with the drug transport systems involving p-glycoprotein (P-gp) and Phase I studies support the adjustment of afatinib dose as tolerated in patients requiring coadministration of P-gp inhibitors/inducers [67,68].…”

Section: Afatinibmentioning

confidence: 99%

“…Afatinib is not metabolised but enzyme-catalysed metabolic reactions and is not an inhibitor or an inducer of the CYP enzymes [67]. In vitro studies have shown that afatinib interacts with the drug transport systems involving p-glycoprotein (P-gp) and Phase I studies support the adjustment of afatinib dose as tolerated in patients requiring coadministration of P-gp inhibitors/inducers [67,68]. Afatinib is dosed once daily and should preferably not be taken with food; Phase I studies have shown that when consumed with a high fat meal exposure to afatinib is reduced [68,69].…”

Section: Afatinibmentioning

confidence: 99%

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Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors

Rolfo

Giovannetti

Hong

et al. 2014

Cancer Treatment Reviews

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a b s t r a c tIntroduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs. Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arise from secondary EGFR mutations. Other resistance-inducing processes include mesenchymal-epithelial transition factor (MET) amplification, epithelial-mesenchymal transformation, phenotypic change from NSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current therapeutic strategies to overcome these EGFR TKI resistance mechanisms focus on the inhibition or blocking of multiple members of the ErbB family. Several molecules which target multiple ErbB receptors are being investigated in NSCLC and other indications including afatinib, an ErbB Family Blocker, as well as dacomitinib and lapatinib. Novel, non-quinazoline, EGFR inhibitors, that also target EGFR activating and resistance (T790M) mutations, are currently under clinical development. Other therapeutic strategies include inhibition of parallel and downstream pathways, using agents which target heat shock protein (HSP)90 or http://dx.doi.org/10.1016/j.ctrv.2014.05.009 0305-7372/Ó 2014 Elsevier Ltd. All rights reserved.Abbreviations: AEG-1, astrocyte elevated gene-1; ALK, anaplastic lymphoma kinase; ATP, adenosine triphosphate; BARD1, BRCA1-associated protein 1; BIM, B-cell lymphoma 2 interacting mediator of cell death; BRAF, v-raf murine sarcoma viral oncogene homolog B1; BRCA1, breast cancer 1, early onset; CNS, central nervous system; CRKL, crk-like protein; DCR, disease control rate; EGFR, epidermal growth factor receptor; EMT, epithelial-mesenchymal transformation; EphB4, ephrin type-B receptor 4; ER, oestrogen receptor; ERK, extracellular-signal-regulated kinases; HER, human epidermal growth factor receptor; HGF, hepatocyte growth factor; HSP90, heat shock protein 90; IGF-1R, insulin-like growth factor 1 receptor; KRAS, Kirsten rat sarcoma viral oncogene homologue; MBP-QP, mutation-biased PCR quenching probe; MEK, mitogen-activated protein kinase; MET, mesenchymal-epithelial transition factor; mRNA, messenger RNA; mTOR, mammalian target of rapamycin; NF-jB, nuclear factor kappa-light-chainenhancer of activated B cells; NSCLC, non-small-cell lung cancer; ORR, overall response rate; OS, overall survival; PARP, poly (ADP-ribose) polymerase; PCR, polymerase chain reaction; PFS, progression free survival; PI3K, phosphoinositide-3-kinase; PIK3CA, phosphoinositide-3-kinase, catalytic, alpha polypeptide; PTEN, phosphatase and tensin homologue; RECIST, Response Evaluation Criteria in Solid Tumours; RR, response rate; SCLC, small-cell lung cancer; TGF, transforming growth factor; TKI, tyrosine kinase inhibitors; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor. E-mail address: christian.rolfo@uza.be (C. Rolfo).Can...

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Pharmacokinetic Drug Interactions of Afatinib with Rifampicin and Ritonavir

Cited by 55 publications

References 21 publications

The Effect of P-Glycoprotein Inhibition and Activation on the Absorption and Serum Levels of Cyclosporine and Tacrolimus in Rats

The Effect of P-Glycoprotein Inhibition and Activation on the Absorption and Serum Levels of Cyclosporine and Tacrolimus in Rats

Tyrosine kinase inhibitors for EGFR- and ALK-mutated non-small cell lung cancer

Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors

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