Article
Pharmacology & Pharmacy
Yuan Xu, Jian Lu, Bingyi Yao, Yuanjin Zhang, Shengbo Huang, Jie Liu, Yanfang Zhang, Yuanqing Guo, Xin Wang
Summary: The combination of fluoxetine and olanzapine significantly increased the plasma concentration of olanzapine, decreased its clearance, and increased tissue exposure in rats, indicating a potential drug-drug interaction. However, in gene knockout rats, the combination did not show similar effects.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Leandro Francisco Pippa, Carolina Pinto Vieira, Juciene Aparecida Caris, Adriana Rocha, Maria Paula Marques, Camile Prates Garcia, Rosamar Eulira Fontes Rezende, Vera Lucia Lanchote
Summary: This study evaluated the activity of OATP1B1, BCRP, and P-gp in patients with chronic HCV infection before and after treatment with direct-acting antiviral agents. The activity of these transporters was found to be reduced in patients with different levels of liver fibrosis, both before and after treatment. Clinicians should take into consideration the treatment response and stage of HCV infection when administering substrates of these transporters with low therapeutic indexes.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(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)
Review
Medicine, General & Internal
Venceslas Bourdin, William Bigot, Anthony Vanjak, Ruxandra Burlacu, Amanda Lopes, Karine Champion, Audrey Depond, Blanca Amador-Borrero, Damien Sene, Chloe Comarmond, Stephane Mouly
Summary: Concomitant administration of multiple drugs can lead to severe drug-drug interactions, increasing the risk of enhanced toxicity and treatment failure. The activity of cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp) plays a critical role in drug clearance, clinical efficacy, and interindividual variability, and is involved in many clinically relevant drug interactions, including those with dexamethasone. The increased use of high doses of dexamethasone during the COVID-19 pandemic highlights the importance of understanding the clinical significance of drug interactions involving dexamethasone in the clinical setting.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Sho Shimazaki, Junko Kuroda, Kenju Shimomura, Shingen Misaka
Summary: The study suggests that measuring the urinary excretion of nadolol can be a sensitive and reliable alternative to plasma pharmacokinetics for the evaluation of P-glycoprotein-mediated drug interactions.
JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Louise Breuil, Sebastien Goutal, Solene Marie, Antonio Del Vecchio, Davide Audisio, Amelie Soyer, Maud Goislard, Wadad Saba, Nicolas Tournier, Fabien Caille
Summary: This study compared the efflux and brain exposure of domperidone and metoclopramide at the blood-brain barrier using PET imaging. The results showed that domperidone had lower penetration and exposure in the brain compared to metoclopramide.
Article
Biochemistry & Molecular Biology
Osama Y. Alshogran, Nour F. Al Ghraiybah, Sayer Al-Azzam
Summary: The study showed that parabens did not significantly affect the PK parameters of digoxin or the mRNA expression of p-gp, suggesting a minimal interaction with p-gp drug substrates.
CURRENT MOLECULAR PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Louise Breuil, Nora Ziani, Sarah Leterrier, Gaelle Hugon, Fabien Caille, Viviane Bouilleret, Charles Truillet, Maud Goislard, Myriam El Biali, Martin Bauer, Oliver Langer, Sebastien Goutal, Nicolas Tournier
Summary: This study investigated the impact of CYP inducers and inhibitors on the brain and plasma kinetics of [C-11]metoclopramide using PET imaging. The results showed that CYP induction or inhibition had negligible effects on the plasma kinetics and metabolism of [C-11]metoclopramide, but ritonavir significantly increased brain penetration.
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, Medicinal
Sarah Lazzaro, Mark A. West, Soraya Eatemadpour, Bo Feng, Manthena V. S. Varma, A. David Rodrigues, Csilla Temesszentandrasi-Ambrus, Peter Kovacs-Hajdu, Zsuzsanna Nerada, Zsuzsanna Gaborik, Chester Costales
Summary: This study evaluated the impact of potential IC50 discrepancies between two commonly utilized assay methods (cell-based and vesicle-based) on P-gp. Non-P-gp substrates showed good correlation between the two methods, while IC50s of P-gp substrates were lower in the vesicle assays. IC50s obtained from two independent laboratories using the same method showed good correlation.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Hamim Zahir, Fumiaki Kobayashi, Cynthia Zamora, Roohi Gajee, Michael S. Gordon, Hani M. Babiker, Qiang Wang, Jonathan Greenberg, Andrew J. Wagner
Summary: Pexidartinib is a moderate inducer of CYP3A and a weak inhibitor of CYP2C9, with no significant effect on CYP2C19-mediated metabolism or P-gp transport. Multiple doses of pexidartinib resulted in decreased AUC(last) of midazolam and increased AUC(last) of tolbutamide, while omeprazole exposure decreased with concurrent administration of pexidartinib and digoxin concentrations slightly increased.
JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Endocrinology & Metabolism
Louise Breuil, Solene Marie, Sebastien Goutal, Sylvain Auvity, Charles Truillet, Wadad Saba, Oliver Langer, Fabien Caille, Nicolas Tournier
Summary: This study investigates differences in vulnerability to P-gp inhibition among radiolabeled substrates and emphasizes the importance of considering partial inhibition of transporter function as a primary criterion in evaluating the sensitivity of radiolabeled substrates to detect moderate but physiologically-relevant changes in transporter function in vivo.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Oncology
Venkatesh Pilla Reddy, Adrian J. Fretland, Diansong Zhou, Shringi Sharma, Buyun Chen, Karthick Vishwanathan, Dermot F. McGinnity, Yan Xu, Joseph A. Ware
Summary: Limited information is available regarding the DDI potential between molecular targeted agents and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy. Adding the BTK inhibitor ibrutinib to R-CHOP therapy may increase toxicity, particularly peripheral neuropathy. However, the addition of acalabrutinib to R-CHOP therapy showed low DDI risk with minimal increase in vincristine-induced peripheral neuropathy.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Lu Liu, Wei Li, Le Yang, Zi-tao Guo, Hao Xue, Ning-jie Xie, Xiao-yan Chen
Summary: Almonertinib, a novel EGFR tyrosine kinase inhibitor, is metabolized by CYP3A, with the major active metabolite being N-desmethyl almonertinib (HAS-719). Co-administration with itraconazole increased almonertinib levels but reduced HAS-719 levels, while rifampicin decreased levels of both almonertinib and HAS-719. Further metabolism of HAS-719 may contribute to its altered pharmacokinetics when combined with rifampicin.
ACTA PHARMACOLOGICA SINICA
(2022)
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)
Letter
Oncology
Hans C. Lee, Noopur S. Raje, Ola Landgren, Vijay V. Upreti, Jin Wang, Ariel A. Avilion, Xuguang Hu, Erik Rasmussen, Gataree Ngarmchamnanrith, Hisaki Fujii, Andrew Spencer
Article
Pharmacology & Pharmacy
Tycho Heimbach, Yuan Chen, Jun Chen, Vaishali Dixit, Neil Parrott, Sheila Annie Peters, Italo Poggesi, Pradeep Sharma, Jan Snoeys, Mohamad Shebley, Guoying Tai, Susanna Tse, Vijay V. Upreti, Ying-Hong Wang, Alice Tsai, Binfeng Xia, Ming Zheng, Andy Z. X. Zhu, Stephen Hall
Summary: The predictive performance of physiologically-based pharmacokinetics (PBPK) models for pharmacokinetics (PK) in renal impairment (RI) and hepatic impairment (HI) populations was evaluated using clinical data from 29 compounds with 106 organ impairment study arms. The results showed high accuracy in predicting AUC ratios for RI, while inaccuracies were more likely to occur in moderate and severe HI cases. PBPK predictions can help determine the need and timing of organ impairment study.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Editorial Material
Pharmacology & Pharmacy
Gerald R. Galluppi, Satjit Brar, Luzelena Caro, Yuan Chen, Nicolas Frey, Hans Peter Grimm, Deanne Jackson Rudd, Chi-Chung Li, Mindy Magee, Arnab Mukherjee, Lee Nagao, Vivek S. Purohit, Amit Roy, Ahmed Hamed Salem, Vikram Sinha, Ahmed A. Suleiman, Kunal S. Taskar, Vijay V. Upreti, Benjamin Weber, Jack Cook
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Medicine, Research & Experimental
Johannes Kast, Sandeep Dutta, Vijay V. Upreti
Summary: Panitumumab is a fully human monoclonal antibody approved for the treatment of wild-type RAS metastatic colorectal cancer. It has a nonlinear pharmacokinetic profile and the approved dosing regimen is weight-based, with no need for dose adjustments based on sex, age, or renal or hepatic impairment.
ADVANCES IN THERAPY
(2021)
Article
Oncology
Michael Z. Liao, Hans Prenen, Sandeep Dutta, Vijay V. Upreti
Summary: The study demonstrated that mild-to-moderate hepatic or renal impairment had no clinically meaningful impact on the pharmacokinetics of panitumumab in patients with mCRC, indicating no need for dose adjustments.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Chunze Li, Rajeev Menon, Markus Walles, Renu Singh, Vijay V. Upreti, Deanna Brackman, Anthony J. Lee, Christopher J. Endres, Seema Kumar, Donglu Zhang, Frank Barletta, Ajit Suri, Dominik Hainzl, Kai H. Liao, Bojan Lalovic, Maribel Beaumont, Peiying Zuo, Andrew P. Mayer, Dong Wei
Summary: ADCs, a rapidly evolving area of drug development, combine the target specificity of monoclonal antibodies with the anticancer activity of small-molecule therapeutics, showing significant promise. The complexity of ADC structure often requires quantification of ADC conjugate, total antibody, and unconjugated payload in drug development. Considerations for drug-drug interactions (DDI) with ADCs may differ from traditional small molecule therapeutics, with a potential for unconjugated payloads to be a victim of DDI.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Oncology
Stergios J. Moschos, Shahneen Sandhu, Karl D. Lewis, Ryan J. Sullivan, Igor Puzanov, Douglas B. Johnson, Haby A. Henary, Hansen Wong, Vijay V. Upreti, Georgina V. Long, Keith T. Flaherty
Summary: Combining AMG 232, a drug targeting the MDM2-p53 interaction, with MAPK inhibitors showed better safety and efficacy compared to using MAPK inhibitors alone in preclinical melanoma models. However, adding AMG 232 did not provide additional clinical benefit in patients with TP53-wild type, MAPKi-naive metastatic melanoma.
INVESTIGATIONAL NEW DRUGS
(2022)
Review
Medicine, Research & Experimental
Johannes Kast, Saeideh Nozohouri, Di Zhou, Marc R. Yago, Po-Wei Chen, Malidi Ahamadi, Sandeep Dutta, Vijay V. Upreti
Summary: Advances in immuno-oncology have led to the development of novel therapies, such as CAR-T cells and TCR-T cells, which utilize the innate immune system to effectively treat solid and non-solid tumors. This review provides insights into the clinical pharmacology aspects of these immuno-therapies, with a focus on CAR-T cells. It summarizes the structure of CAR-T cells, the effects and toxicities observed in clinical trials, risk mitigation strategies, dose selection approaches, and cellular kinetics. Additionally, it discusses quantitative approaches and modeling techniques used in the development of CAR-T cell therapies.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Malidi Ahamadi, Johannes Kast, Po-Wei Chen, Xiaojun Huang, Sandeep Dutta, Vijay V. V. Upreti
Summary: T-VEC is a first-in-class oncolytic virotherapy approved for unresectable melanoma recurrent. Our analysis found that viral infection rate greatly influences T-VEC treatment efficacy, increasing T-VEC dose resulted in a 12% increase in response, and the ratio of resting innate immune cells to the death rate of innate immune impacts T-VEC treatment efficacy at the systemic level.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Marc R. R. Yago, Khamir Mehta, Maitreyee Bose, Sharvari Bhagwat, Vivek S. S. Chopra, Sandeep Dutta, Vijay V. V. Upreti
Summary: A pharmacokinetic/pharmacodynamic model was built to compare the effectiveness of once-weekly and twice-weekly use of the irreversible proteasome inhibitor carfilzomib. The results demonstrated that both dosing regimens had comparable proteasome inhibition and clinical response.
CLINICAL PHARMACOKINETICS
(2023)
Article
Pharmacology & Pharmacy
Xinwen Zhang, Annie Lumen, Hansen Wong, Jamie Connarn, Sandeep Dutta, Vijay V. Upreti
Summary: This study developed a mechanistic-physiologically-based pharmacokinetic (PBPK) platform model that accurately predicts the pharmacokinetics of adult and pediatric patients in both liquid and solid tumor indications. The model provides guidance for optimal dose and dosing regimen selection of Bispecific T cell engagers (Bi-TCEs) and accelerates their clinical development.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Hardik Mody, Ken Ogasawara, Xu Zhu, Dale Miles, Prathap Nagaraja Shastri, Jochem Gokemeijer, Michael Z. Liao, Sreeneeranj Kasichayanula, Tong-Yuan Yang, Nagendra Chemuturi, Swati Gupta, Vibha Jawa, Vijay V. Upreti
Summary: CAR-T cell therapies have revolutionized the treatment of hematological malignancies and are making progress in solid tumor indications. Recent developments include the clinical development of allogeneic CAR-T therapies that can overcome the time-consuming wait for autologous CAR-T therapies. To accelerate the development of these life-saving therapies, experts formed a joint working group under the IQ consortium to provide best practices and considerations for clinical pharmacology and pharmacometric aspects of CAR-T and TCR-T cell therapies.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Di Zhou, Lauren A. Byers, Beate Sable, Marie-Anne Damiette Smit, Nooshin Hashemi Sadraei, Sandeep Dutta, Vijay V. Upreti
Summary: This article presents the clinical pharmacology profile of AMG 119, a CAR-T cell therapy targeting DLL3, in patients with relapsed/refractory small cell lung cancer. The study demonstrates robust cellular expansion and persistence of AMG 119, with favorable safety profile at tested doses. The data in this article is encouraging and supports the potential of CAR-T cell therapy in solid tumor treatment.
JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Review
Medicine, Research & Experimental
Tong-yuan Yang, Manuela Braun, Wibke Lembke, Fraser McBlane, John Kamerud, Stephen DeWall, Edit Tarcsa, Xiaodong Fang, Lena Hofer, Uma Kavita, Vijay V. Upreti, Swati Gupta, LiNa Loo, Alison J. Johnson, Rakesh Kantilal Chandode, Kay-Gunnar Stubenrauch, Maya Vinzing, Cindy Q. Xia, Vibha Jawa
Summary: Immunogenicity poses a challenge to the evaluation of efficacy and safety of AAV gene therapies. Various clinical mitigation strategies have been employed to reduce immunogenicity and achieve desired efficacy, reduce toxicity, or treat more patients who have pre-existing immunity to AAV vectors.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Pharmacology & Pharmacy
Michael Z. Liao, Marloes Berkhout, Hans Prenen, Sandeep Dutta, Vijay V. Upreti
CLINICAL PHARMACOLOGY-ADVANCES AND APPLICATIONS
(2020)