Objective: The ABCB1 haplotype combinations have been demonstrated to be associated with epilepsy treatment outcomes. The aim of this study is to investigate whether ABCB1 haplotype combinations would affect P-glycoprotein (Pgp) function and impact the clinical responses of antiepileptic drugs (AEDs).
Methods And Results: Transport of substrate rhodamine 123 and calcein-AM by human Pgp carrying 12 haplotype combinations of 1236C>T, 2677G>T/A and 3435C>T were assayed in the absence and presence of known inhibitors and AEDs. The inhibitory potency of the tested drugs from the dose-response relationships was cyclosporin A>verapamil> phenytoin> carbamazepine> lamotrigine>phenobarbital>valproic acid, levetiracetam, gabapentin. The silent polymorphisms combination (1236T-3435T) and triple haplotypes (1236T-2677A/T-3435T) resulted in profoundly less effective inhibition against substrates with significantly lower intracellular substrate concentration. These results confirmed that ABCB1 polymorphisms were associated with clinical responses of AEDs.
Conclusion: Our findings demonstrated that human ABCB1 polymorphisms may alter the interactions between Pgp and substrates, and provided functional evidence for ABCB1 haplotypes-associated epilepsy treatment responses.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/FPC.0b013e3282f85e36 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Lupus disease activity state and Foxp3 gene polymorphism.
Egypt J Immunol
January 2025
Department of Medical Microbiology and Immunology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
The autoimmune disease systemic lupus erythematosus (SLE) is presented with many clinical symptoms. The transcription factor fork head box protein 3 (Foxp3) is expressed on regulatory T (T-reg) cells and essential for its development and function. Functional single-nucleotide polymorphisms (SNPs) in the Foxp3-3279 (rs3761548 C/A) gene influence SLE pathogenesis.
View Article and Find Full Text PDFSurgical and Pathological Results Following Neoadjuvant Nivolumab and Platinum-Based Chemotherapy for Locally Advanced Resectable NSCLC: A Multicentre Real-World Series From England.
Clin Lung Cancer
December 2024
Department of Thoracic Surgery, Liverpool Heart and Lung Hospital, Liverpool, UK.
Background: To evaluate the real-world surgical and pathological outcomes following neoadjuvant nivolumab in combination with chemotherapy in a multicentre national cohort of patients.
Methods: Retrospective analysis on consecutive patients treated in three tertiary referral hospitals in UK with neoadjuvant chemotherapy and immunotherapy (nivolumab) for stage II-IIIB nonsmall cell lung cancer (March 2023-May 2024). Surgical and pathological outcomes were assessed.
Development of TAR-200: A novel targeted releasing system designed to provide sustained delivery of gemcitabine for patients with bladder cancer.
Urol Oncol
January 2025
Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital, Milan, Italy; Department of Medical Oncology, IRCCS San Raffaele University, Milan, Italy.
Treatment options for recurrent high-risk non-muscle-invasive bladder cancer (HR NMIBC) and muscle-invasive bladder cancer (MIBC) are limited, highlighting a need for clinically effective, accessible, and better-tolerated alternatives. In this review we examine the clinical development program of TAR-200, a novel targeted releasing system designed to provide sustained intravesical delivery of gemcitabine to address the needs of patients with NMIBC and of those with MIBC. We describe the concept and design of TAR-200 and the clinical development of this gemcitabine intravesical system in the SunRISe portfolio of studies.
View Article and Find Full Text PDFObjective: To update and establish content validity for the Checklist of NICU Caregiver Behaviors.
Design: Structured literature review and Delphi analysis.
Setting/local Problem: Neonates born prematurely or who are sick in the NICU are frequently exposed to harmful stimuli that can affect brain development and result in adverse neurodevelopmental outcomes.
AP2M1 as the potential biomarker for prediction of the response of atopic dermatitis to Dupilumab therapy: Multi-omics analysis and evidence.
Int J Biol Macromol
January 2025
Department of Dermatology, the Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin, China. Electronic address:
Many atopic dermatitis (AD) patients have suboptimal responses to Dupilumab therapy. This study identified key genes linked to this resistance using multi-omics approaches to benefit more patients. We selected a prospective cohort of 54 CE treated with Dupilumab from the GEO database.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!