Article
Pharmacology & Pharmacy
Burak Ozgur, Lasse Saaby, Christian Janfelt, Kristine Langthaler, Elin Eneberg, Anne-Marie Jacobsen, Lassina Badolo, Dino Montanari, Birger Brodin
Summary: The iP-gp cell model was found to be a sensitive and useful screening tool for identifying potential substrates of human P-glycoprotein, with results correlating with in vivo studies.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Holger Fischer, Claudia Senn, Mohammed Ullah, Carina Cantrill, Franz Schuler, Li Yu
Summary: The study suggests the use of a novel in vitro model, AP-ER, to measure P-glycoprotein-mediated transport, showing that AP-ER predicts cerebrospinal fluid concentrations better than traditional ER for certain compounds and the AP-ER/ER ratios may be conserved across different species.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Jocelyn Yabut, Robert Houle, Shubing Wang, Andy Liaw, Ravi Katwaru, Hannah Collier, Lucinda Hittle, Xiaoyan Chu
Summary: This study conducted comprehensive calibration of two in vitro P-gp inhibition models, vesicular uptake and bidirectional transport, to predict DDIs. The results suggest that IC50 values obtained from vesicular inhibition with a refined threshold of I-2/IC50 >= 25.9 provide comparable predictive power over those in LLC-MDR1 cells. Therefore, the vesicular P-gp inhibition method is recommended as the preferred option due to its simplicity, lower variability, higher assay throughput, and more direct estimation of in vitro kinetic parameters.
DRUG METABOLISM AND DISPOSITION
(2022)
Article
Chemistry, Medicinal
Ricardo G. Teixeira, Iris C. Salaroglio, Nuno F. B. Oliveira, Joao G. N. Sequeira, Xavier Fontrodona, Isabel Romero, Miguel Machuqueiro, Ana Isabel Tomaz, M. Helena Garcia, Chiara Riganti, Andreia Valente
Summary: The urgent need to find more effective and selective drugs to overcome cancer multidrug resistance has led to the development and characterization of a new series of ruthenium-cyclopentadienyl (RuCp) compounds. These compounds were found to exhibit better cytotoxicity than the first-line chemotherapeutic drug cisplatin in non-small cell lung cancer cells. Furthermore, two specific compounds were shown to inhibit the activity of P-gp and MRP1 efflux pumps, providing potential candidates to circumvent cancer multidrug resistance.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Jessica Chu, Erika Panfen, Linna Wang, Anthony Marino, Xue-Qing Chen, R. Marcus Fancher, Raviraj Landage, Omprakash Patil, Salil Dileep Desai, Devang Shah, Yongjun Xue, Michael Sinz, Hong Shen
Summary: The aim of this study was to evaluate the differences between intestinal and systemic P-gp and BCRP in drug disposition. The results showed that ECD is a potent inhibitor of intestinal P-gp and BCRP. The inhibition potential of ECD towards human and animal P-gp and BCRP was assessed in vitro and in vivo.
PHARMACEUTICAL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Lara Garcia-Varela, Pascalle Mossel, Pablo Aguiar, Daniel A. Vazquez-Matias, Aren van Waarde, Antoon T. M. Willemsen, Anna L. Bartels, Nicola A. Colabufo, Rudi A. J. O. Dierckx, Philip H. Elsinga, Gert Luurtsema
Summary: This study found that small changes in P-gp function caused by low doses of tariquidar could be detected by [F-18]MC225-K-1 values, confirming the high sensitivity of the radiotracer.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Biochemistry & Molecular Biology
Dhanamjai Penta, Priya Mondal, Jagadish Natesh, Syed Musthapa Meeran
Summary: The study demonstrates that diindolylmethane can enhance the efficacy of Centchroman in treating breast cancer by modulating drug efflux transporters, inhibiting cell proliferation, inducing apoptosis, and hindering stemness of cancer cells.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2021)
Article
Instruments & Instrumentation
Pranav Shah, Kejal Chavda, Bhavin Vyas, Shailaja Patel
Summary: The development of Linagliptin solid lipid nanoparticles (LGP-SLNs) aimed to improve its oral bioavailability by using poloxamer 188 and Tween 80 as P-gp inhibitors. Experimental results showed that LGP-SLNs exhibited higher relative bioavailability and better glucose reduction effects in vivo.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Kunal S. Taskar, Xinning Yang, Sibylle Neuhoff, Mitesh Patel, Kenta Yoshida, Mary F. Paine, Kim L. R. Brouwer, Xiaoyan Chu, Yuichi Sugiyama, Jack Cook, Joseph W. Polli, Imad Hanna, Yurong Lai, Maciej Zamek-Gliszczynski
Summary: This article discusses the role of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in drug-drug interactions, drug absorption, and brain penetration. Based on clinical evidence, the article suggests that inhibition of P-gp or BCRP in the liver or kidneys has limited clinical implications on drug disposition.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Pharmacology & Pharmacy
Sachin Rathod, Heta Desai, Rahul Patil, Jayant Sarolia
Summary: This article discusses the significance of studying P-glycoprotein in drug delivery and highlights the effective reversal of P-gp inhibition using nonionic surfactants. Nonionic surfactants, being inert, non-toxic, and efficient, show potential as P-gp inhibitors and improve drug absorption and bioavailability through various mechanisms.
Article
Pharmacology & Pharmacy
Tingting Zhao, Xuening Li, Yanwei Chen, Jie Du, Xiaodong Chen, Dalong Wang, Liyan Wang, Shan Zhao, Changyuan Wang, Qiang Meng, Huijun Sun, Kexin Liu, Jingjing Wu
Summary: Cancer patients are at high risk of thrombotic diseases, but anticoagulant therapy increases bleeding risks. This study explores the combination safety of rivaroxaban with tyrosine kinase inhibitors (TKIs) and finds significant drug-drug interactions in different combinations. Imatinib increases bleeding risks while sunitinib reduces therapeutic efficacy. Therefore, caution should be exercised in the coadministration of rivaroxaban and TKIs to avoid harmful interactions.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lavanya Bolla, Pratima Srivastava, Velayutham Ravichandiran, Satheesh Kumar Nanjappan
Summary: Garcinol, a compound found in Garcinia indica and Garcinia cambogia, has been shown to exhibit strong inhibitory effects on various drug-metabolizing CYP isozymes. This may lead to herb-drug interactions altering pharmacokinetic parameters in vivo. Molecular docking studies confirmed the inhibitory activity by binding to active sites of CYPs. Further research is needed to fully understand the potential implications for clinical use.
Article
Biochemistry & Molecular Biology
Yunmoon Oh, Jin-Sol Lee, Ji Sun Lee, Jae Hyeon Park, Hyung Sik Kim, Sungpil Yoon
Summary: This study found that co-treatment with the JAK2 inhibitor fedratinib can enhance cytotoxicity in P-gp-overexpressing drug-resistant cancer cells when used in combination with the anticancer drug vinicristine. The cytotoxic effects are specific to resistant cancer cells and are mediated through cell cycle regulation and induction of apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Edward Price, J. Cory Kalvass, David DeGoey, Balakrishna Hosmane, Stella Doktor, Kelly Desino
Summary: This study evaluated different models for predicting human intestinal absorption data, providing a resource for DMPK scientists and medicinal/computational chemists to enhance their understanding of the utility and applications of permeability and absorption models for academia and industry.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Hiroki Morishita, Liyanage Manosika Buddhini Perera, Xieyi Zhang, Kenta Mizoi, Masa-aki Ito, Kentaro Yano, Takuo Ogihara
Summary: The combined use of Pimozide with other drugs may increase the risk of cardiac arrest. This study investigated the accumulation of Pimozide in cardiomyocytes and its inhibitory effect on cardiac channels, showing that Pimozide accumulation is influenced by other drugs, leading to an increased risk of channel inhibition.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)