Clinical assessment of momelotinib drug-drug interactions via CYP3A metabolism and transporters
Clin Transl Sci. 2024 Apr;17(4):e13799. doi: 10.1111/cts.13799.ABSTRACTMomelotinib-approved for treatment of myelofibrosis in adults with anemia-and its major active metabolite, M21, were assessed as drug-drug interaction (DDI) victims with a strong cytochrome P450 (CYP) 3A4 inhibitor (multiple-dose ritonavir), an organic anion transporting polypeptide (OATP) 1B1/1B3 inhibitor (single-dose rifampin), and a strong CYP3A4 inducer (multiple-dose rifampin). Momelotinib DDI perpetrator potential (multiple-dose) was evaluated with CYP3A4 and breast cancer resistance protein (BCRP) substrates (midazolam and rosuvastatin, respecti...
Source: Clinical Genitourinary Cancer - April 18, 2024 Category: Cancer & Oncology Authors: Yu Liu Ho Pete Gorycki Geraldine Ferron-Brady Paul Martin Georgios Vlasakakis Source Type: research
Clinical assessment of momelotinib drug-drug interactions via CYP3A metabolism and transporters
Clin Transl Sci. 2024 Apr;17(4):e13799. doi: 10.1111/cts.13799.ABSTRACTMomelotinib-approved for treatment of myelofibrosis in adults with anemia-and its major active metabolite, M21, were assessed as drug-drug interaction (DDI) victims with a strong cytochrome P450 (CYP) 3A4 inhibitor (multiple-dose ritonavir), an organic anion transporting polypeptide (OATP) 1B1/1B3 inhibitor (single-dose rifampin), and a strong CYP3A4 inducer (multiple-dose rifampin). Momelotinib DDI perpetrator potential (multiple-dose) was evaluated with CYP3A4 and breast cancer resistance protein (BCRP) substrates (midazolam and rosuvastatin, respecti...
Source: Clinical Breast Cancer - April 18, 2024 Category: Cancer & Oncology Authors: Yu Liu Ho Pete Gorycki Geraldine Ferron-Brady Paul Martin Georgios Vlasakakis Source Type: research
Clinical assessment of momelotinib drug-drug interactions via CYP3A metabolism and transporters
Clin Transl Sci. 2024 Apr;17(4):e13799. doi: 10.1111/cts.13799.ABSTRACTMomelotinib-approved for treatment of myelofibrosis in adults with anemia-and its major active metabolite, M21, were assessed as drug-drug interaction (DDI) victims with a strong cytochrome P450 (CYP) 3A4 inhibitor (multiple-dose ritonavir), an organic anion transporting polypeptide (OATP) 1B1/1B3 inhibitor (single-dose rifampin), and a strong CYP3A4 inducer (multiple-dose rifampin). Momelotinib DDI perpetrator potential (multiple-dose) was evaluated with CYP3A4 and breast cancer resistance protein (BCRP) substrates (midazolam and rosuvastatin, respecti...
Source: Clinical Genitourinary Cancer - April 18, 2024 Category: Cancer & Oncology Authors: Yu Liu Ho Pete Gorycki Geraldine Ferron-Brady Paul Martin Georgios Vlasakakis Source Type: research
Ritonavir: 25 Years ’ Experience of Concomitant Medication Management. A Narrative Review
AbstractRitonavir is a potent inhibitor of the cytochrome P450 3A4 enzyme and is commonly used as a pharmacokinetic (PK) enhancer in antiviral therapies because it increases bioavailability of concomitantly administered antivirals. Decades of experience with ritonavir-enhanced HIV therapies and, more recently, COVID-19 therapies demonstrate that boosting doses of ritonavir are well tolerated, with an established safety profile. The mechanisms of PK enhancement by ritonavir result in the potential for drug –drug interactions (DDIs) with several classes of drugs, thus making co-medication management an important considerat...
Source: Infectious Diseases and Therapy - April 12, 2024 Category: Infectious Diseases Source Type: research
Effectiveness of nirmatrelvir-ritonavir versus azvudine for adult inpatients with severe or critical COVID-19
CONCLUSION: Paxlovid and azvudine had similar effectiveness on in-hospital all-cause mortality and hospital length of stay. Compared with the azvudine group, after 7 days of therapy, the degree of decline in SOFA score was significantly higher in the Paxlovid group. These findings need to be verified in larger prospective studies or randomised controlled trials.PMID:38599779 | DOI:10.1136/bmjresp-2023-001944 (Source: Respiratory Care)
Source: Respiratory Care - April 10, 2024 Category: Respiratory Medicine Authors: Huan Zhang Tan Xiaojiao Junjun Chen Zheng Zhang Chenxi Wang Haiqing Shi Yao Li Jianbo Li Yan Kang Xiaodong Jin Xuelian Liao Source Type: research
Prevalence and Management of Medication Interactions with Nirmatrelvir-Ritonavir at a Large Urban Academic Medical Center: An Observational Study
(Source: Journal of General Internal Medicine)
Source: Journal of General Internal Medicine - April 10, 2024 Category: Internal Medicine Source Type: research
Nirmatrelvir –Ritonavir Reduced Mortality in Hospitalized Patients with COVID-19 During the Omicron Outbreak: Real-World Evidence from Beijing
(Source: Infection and Drug Resistance)
Source: Infection and Drug Resistance - April 8, 2024 Category: Infectious Diseases Tags: Infection and Drug Resistance Source Type: research
SARS-CoV-2 M < sup > pro < /sup > oligomerization as a potential target for therapy
In this study, we utilized biochemical, structural, and molecular modelling approaches to explore Mpro dimerization. We evaluated critical residues, specifically Arg4 and Arg298, that are essential for dimerization. Our results show that changes in the oligomerization state of Mpro directly affect its enzymatic activity and dimerization propensity. We discovered a synergistic relationship influencing dimer formation, involving both intra- and intermolecular interactions. These findings highlight the potential for developing allosteric inhibitors targeting Mpro, offering promising new directions for therapeutic strategies.P...
Source: International Journal of Biological Macromolecules - April 6, 2024 Category: Biochemistry Authors: Kinga Lis Jacek Plewka Filipe Menezes Ewa Bielecka Yuliya Chykunova Katarzyna Pustelny Stephan Niebling Angelica Struve Garcia Maria Garcia-Alai Grzegorz M Popowicz Anna Czarna Tomasz Kantyka Krzysztof Pyrc Source Type: research
SARS-CoV-2 M < sup > pro < /sup > oligomerization as a potential target for therapy
In this study, we utilized biochemical, structural, and molecular modelling approaches to explore Mpro dimerization. We evaluated critical residues, specifically Arg4 and Arg298, that are essential for dimerization. Our results show that changes in the oligomerization state of Mpro directly affect its enzymatic activity and dimerization propensity. We discovered a synergistic relationship influencing dimer formation, involving both intra- and intermolecular interactions. These findings highlight the potential for developing allosteric inhibitors targeting Mpro, offering promising new directions for therapeutic strategies.P...
Source: International Journal of Biological Macromolecules - April 6, 2024 Category: Biochemistry Authors: Kinga Lis Jacek Plewka Filipe Menezes Ewa Bielecka Yuliya Chykunova Katarzyna Pustelny Stephan Niebling Angelica Struve Garcia Maria Garcia-Alai Grzegorz M Popowicz Anna Czarna Tomasz Kantyka Krzysztof Pyrc Source Type: research
Nirmatrelvir and ritonavir combination against COVID ‐19 caused by omicron BA.2.2 in the elderly: A single‐center large observational study
ConclusionsThese findings suggest that administering nirmatrelvir –ritonavir within 10 days of symptom onset could potentially reduce the time it takes for SARS-CoV-2-infected patients to negative RT-PCR results, thereby expanding the current usage guidelines for nirmatrelvir–ritonavir. (Source: Immunity, Inflammation and Disease)
Source: Immunity, Inflammation and Disease - April 5, 2024 Category: Allergy & Immunology Authors: Can Chen,
Ranyi Li,
Shuliang Xing,
Lei Cao,
Yue Qu,
Qianzhou Lv,
Xiaoyu Li,
Zhangzhang Chen Tags: ORIGINAL ARTICLE Source Type: research
News at a glance: Giant telescope camera complete, limits to Paxlovid benefits, and missing battlefield bones
ASTRONOMY
Biggest ever digital camera heads to Chile
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Researchers at the SLAC National Accelerator Laboratory have finished building the biggest ever astronomical camera. It will create a movie of the universe, imaging the whole southern sky in unprecedented detail every 3 days.
Jacqueline Ramseyer Orrell/SLAC National Accelerator Laboratory
Researchers install the first of 21 arrays of image sensors that together make up the camer...
Source: Science of Aging Knowledge Environment - April 4, 2024 Category: Geriatrics Source Type: research
The effectiveness of novel oral antiviral treatment for non-hospitalized high-risk patients with COVID-19 during predominance of omicron XBB subvariants
CONCLUSION: The use of novel oral antiviral including NMV-r or MOV can be associated with a lower risk of all-cause hospitalization, or death in non-hospitalized high-risk patients with COVID-19 during Omicron XBB wave.PMID:38568820 | DOI:10.1080/14787210.2024.2339398 (Source: Expert Review of Anti-Infective Therapy)
Source: Expert Review of Anti-Infective Therapy - April 3, 2024 Category: Infectious Diseases Authors: Chi-Kuei Hsu Wan-Hsuan Hsu Bo-Wen Shiau Ya-Wen Tsai Jheng-Yan Wu Ting-Hui Liu Po-Yu Huang Min-Hsiang Chuang Chih-Cheng Lai Source Type: research
Nirmatrelvir-Ritonavir Drug Interactions Lead to Multi-Organ Dysfunction in a Lung Transplant Recipient
Introduction: Nirmatrelvir-ritonavir (Paxlovid) therapy for treatment of mild to moderate COVID-19 in lung transplant patients can interact with tacrolimus leading to drug toxicity and organ damage. The appropriate use of Paxlovid in this patient population is of paramount importance. (Source: The Journal of Heart and Lung Transplantation)
Source: The Journal of Heart and Lung Transplantation - April 1, 2024 Category: Transplant Surgery Authors: , M. Pon, W. Zaidi, R. Lee, D. Razia, A. Arjuna Source Type: research
