ArticleClinical pharmacology and therapeutics2020
P-Glycoprotein Inhibition Exacerbates Paclitaxel Neurotoxicity in Neurons and Patients With Cancer.
Article in Clinical pharmacology and therapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- Pharmacokinetic interaction between atorvastatin and fixed-dose combination of sofosbuvir/ledipasvir in healthy male Egyptian volunteers.European journal of clinical pharmacology · 2021Trial
- Breaking the Efflux Barrier: P-Glycoprotein and Emerging Strategies to Overcome Multidrug Resistance in Cancer.Cancers · 2026Review
- Article
- Mechanistic insights into taxane-induced psychiatric adverse events: a global pharmacovigilance and experimental investigation.Molecular psychiatry · 2026Article
- The potential role of COX-2/PGs signaling pathway in epileptogenesis and associated neuroinflammation: collusions or serendipity.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- The Molecular and Clinical Impact of Atorvastatin Exposure on Paclitaxel Neurotoxicity in Sensory Neurons and Cancer Patients.Basic & clinical pharmacology & toxicology · 2025Article
- Crossing the blood-brain barrier: emerging therapeutic strategies for neurological disease.The Lancet. Neurology · 2025Review
- IFN-γ reprograms cardiac microvascular endothelial cells to mediate doxorubicin transport and influences the sensitivity of mice to doxorubicin-induced cardiotoxicity.Experimental & molecular medicine · 2025Article
- Review
- Drug resistance in ovarian cancer: from mechanism to clinical trial.Molecular cancer · 2024Review
- Cytochrome P450 Oxidoreductase (POR) Associated with Severe Paclitaxel-Induced Peripheral Neuropathy in Patients of European Ancestry from ECOG-ACRIN E5103.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Microglia are implicated in the development of paclitaxel chemotherapy-associated cognitive impairment in female mice.Brain, behavior, and immunity · 2023Article
- Phosphosulindac (OXT-328) prevents and reverses chemotherapy induced peripheral neuropathy in mice.Frontiers in neuroscience · 2023Article
- The Impact of P-Glycoprotein on Opioid Analgesics: What's the Real Meaning in Pain Management and Palliative Care?International journal of molecular sciences · 2022Review
- Multidrug Resistance of Cancer Cells and the Vital Role of P-Glycoprotein.Life (Basel, Switzerland) · 2022Review
- Nanomedicine to Overcome Multidrug Resistance Mechanisms in Colon and Pancreatic Cancer: Recent Progress.Cancers · 2021Review
- Role for Drug Transporters in Chemotherapy-Induced Peripheral Neuropathy.Clinical and translational science · 2021Review
- New Evidence for P-gp-Mediated Export of Amyloid-β PEPTIDES in Molecular, Blood-Brain Barrier and Neuronal Models.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Paclitaxel-induced peripheral neuropathy (PIPN) is a common and dose-limiting adverse event. The role of P-glycoprotein (P-gp) in the neuronal efflux of paclitaxel was assessed using a translational approach. SH-SY5Y cells were differentiated to neurons and paclitaxel toxicity in the absence and presence of a P-gp inhibitor was determined. Paclitaxel caused marked dose-dependent toxicity in SH-SY5Y-derived neurons. Paclitaxel neurotoxicity was exacerbated with concomitant P-gp inhibition by valspodar and verapamil, consistent with increased intracellular accumulation of paclitaxel. Patients with cancer treated with paclitaxel and P-gp inhibitors had a 2.4-fold (95% confidence interval (CI) 1.3-4.3) increased risk of peripheral neuropathy-induced dose modification while a 4.7-fold (95% CI 1.9-11.9) increased risk for patients treated with strong P-gp inhibitors was observed, and a 7.0-fold (95% CI 2.3-21.5) increased risk in patients treated with atorvastatin. Atorvastatin also increased neurotoxicity by paclitaxel in SH-SY5Y-derived neurons. Clinicians should be aware that comedication with P-gp inhibitors may lead to increased risk of PIPN.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.