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Article ; Online: A paradigm shift in cancer research based on integrative multi-omics approaches: glutaminase serves as a pioneering cuproptosis-related gene in pan-cancer.

Shi, Hai-Hong / Mugaanyi, Joseph / Lu, Changjiang / Li, Yang / Huang, Jing / Dai, Lei

2024 Volume 24, Issue 1, Page(s) 213

Abstract: Background: Cuproptosis is a newly identified form of unprogrammed cell death. As a pivotal metabolic regulator, glutaminase (GLS) has recently been discovered to be linked to cuproptosis. Despite this discovery, the oncogenic functions and mechanisms ... ...

Abstract	Background: Cuproptosis is a newly identified form of unprogrammed cell death. As a pivotal metabolic regulator, glutaminase (GLS) has recently been discovered to be linked to cuproptosis. Despite this discovery, the oncogenic functions and mechanisms of GLS in various cancers are still not fully understood. Methods: In this study, a comprehensive omics analysis was performed to investigate the differential expression levels, diagnostic and prognostic potential, correlation with tumor immune infiltration, genetic alterations, and drug sensitivity of GLS across multiple malignancies. Results: Our findings revealed unique expression patterns of GLS across various cancer types and molecular subtypes of carcinomas, underscoring its pivotal role primarily in energy and nutrition metabolism. Additionally, GLS showed remarkable diagnostic and prognostic performance in specific cancers, suggesting its potential as a promising biomarker for cancer detection and prognosis. Furthermore, we focused on uterine corpus endometrial carcinoma (UCEC) and developed a novel prognostic model associated with GLS, indicating a close correlation between GLS and UCEC. Moreover, our exploration into immune infiltration, genetic heterogeneity, tumor stemness, and drug sensitivity provided novel insights and directions for future research and laid the foundation for high-quality verification. Conclusion: Collectively, our study is the first comprehensive investigation of the biological and clinical significance of GLS in pan-cancer. In our study, GLS was identified as a promising biomarker for UCEC, providing valuable evidence and a potential target for anti-tumor therapy. Overall, our findings shed light on the multifaceted functions of GLS in cancer and offer new avenues for further research.
MeSH term(s)	Humans ; Glutaminase/genetics ; Multiomics ; Carcinoma ; Research ; Biomarkers
Chemical Substances	Glutaminase (EC 3.5.1.2) ; Biomarkers
Language	English
Publishing date	2024-04-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2050444-5
ISSN	1472-6874 ; 1472-6874
ISSN (online)	1472-6874
ISSN	1472-6874
DOI	10.1186/s12905-024-03061-8
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Article ; Online: Molecular characterization of a novel 83.9-kb deletion of the α-globin upstream regulatory elements by long-read sequencing.

Feng, Jianjiang / Mao, Aiping / Lu, Ye / Shi, Haihong / Meng, Wanli / Liang, Chen

Blood cells, molecules & diseases

2023 Volume 103, Page(s) 102764

Abstract: Inherited deletions of upstream regulatory elements of α-globin genes give rise to α-thalassemia, which is an autosomal recessive monogenic disease. However, conventional thalassemia target diagnosis often fails to identify these rare deletions. Here we ... ...

Abstract	Inherited deletions of upstream regulatory elements of α-globin genes give rise to α-thalassemia, which is an autosomal recessive monogenic disease. However, conventional thalassemia target diagnosis often fails to identify these rare deletions. Here we reported a family with two previous pregnancies of Hb Bart's hydrops fetalis and was seeking for prenatal diagnosis during the third pregnancy. Both parents had low level of Hemoglobin A2 indicating α-thalassemia. Conventional Gap-PCR and PCR-reverse dot blot showed the father carried -
MeSH term(s)	Pregnancy ; Female ; Humans ; Infant ; alpha-Thalassemia/diagnosis ; alpha-Thalassemia/genetics ; alpha-Globins/genetics ; Prenatal Diagnosis/methods ; Hydrops Fetalis/genetics ; Polymerase Chain Reaction/methods ; Hemoglobins, Abnormal
Chemical Substances	alpha-Globins ; Hemoglobins, Abnormal
Language	English
Publishing date	2023-06-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1237083-6
ISSN	1096-0961 ; 1079-9796
ISSN (online)	1096-0961
ISSN	1079-9796
DOI	10.1016/j.bcmd.2023.102764
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Article ; Online: The Diagnostic Value of Triggering Receptor Expressed on Myeloid Cells-1 in Post-Traumatic Bacterial Endophthalmitis.

Tang, Qiuyang / He, Mengxuan / Zhang, Shudan / Zhang, Junfang / Yang, Ling / Shi, Haihong

Investigative ophthalmology & visual science

2023 Volume 64, Issue 5, Page(s) 4

Abstract: Purpose: To determine whether soluble-triggering receptor expressed on myeloid cells-1 (sTREM-1) could serve as a reliable diagnostic biomarker of post-traumatic bacterial endophthalmitis (PTBE).: Methods: Thirty-two patients (32 eyes) clinically ... ...

Abstract	Purpose: To determine whether soluble-triggering receptor expressed on myeloid cells-1 (sTREM-1) could serve as a reliable diagnostic biomarker of post-traumatic bacterial endophthalmitis (PTBE). Methods: Thirty-two patients (32 eyes) clinically diagnosed having PTBE were further divided into a culture-positive (CP) group and a culture-negative (CN) group. Sixty-two patients (62 eyes) without traumatic endophthalmic infection were also enrolled. Twenty-one eyes from 11 donors without globe ocular injuries were included as control group. Vitreous sTREM-1 levels were detected by ELISA. The expression and tissue distribution of TREM-1 were revealed by immunohistochemistry. The diagnostic value of sTREM-1 was determined by receiver operating characteristic curve (ROC). The correlation between sTREM-1 concentration and final best-corrected visual acuity (FBCVA) and Peyman endophthalmitis score (PES) were also assessed. Results: The vitreous sTREM-1 level in the PTBE group was higher than that in noninfected group and control group (P < 0.05). No remarkable difference was found between the CP group and the CN group in vitreous sTREM-1 levels (P > 0.05). No remarkable difference was found between the noninfected group and the control group (P > 0.05). No remarkable difference in TREM-1 level was found before and after intravitreal antibiotics (P > 0.05). TREM-1 was selectively highly expressed on the surface of cell membrane of neutrophils and monocytes/macrophages infiltrated in vitreous and uveal of the PTBE group. The area under the ROC curve (AUC) was 0.79 (>0.75), with a medium diagnostic efficiency. The sensitivity and specificity of sTREM-1 to differentiate PTBE from the noninfected intraocular condition were 62.50% and 86.25% separately. A cutoff value >524.50 pg/mL for sTREM-1 was predicted to be PTBE. Vitreous sTREM-1 levels in PTBE group were positively correlated with PES (r = 0.428, P < 0.05). However, sTREM-1 levels and FBCVA did not significantly correlate with one another (P > 0.05). Conclusions: The sTREM-1 was a promising diagnostic biomarker of PTBE, especially CN-PTBE. Vitreous sTREM-1 levels were linked with intraocular inflammation levels and severity of PTBE.
MeSH term(s)	Humans ; Triggering Receptor Expressed on Myeloid Cells-1 ; Membrane Glycoproteins/metabolism ; Receptors, Immunologic/metabolism ; Biomarkers ; Endophthalmitis/diagnosis
Chemical Substances	Triggering Receptor Expressed on Myeloid Cells-1 ; Membrane Glycoproteins ; Receptors, Immunologic ; Biomarkers
Language	English
Publishing date	2023-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.64.5.4
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Article ; Online: Erratum to "A two-microRNA signature predicts the progression of male thyroid cancer".

Liu, Bingyang / Shi, Haihong / Qiu, Weigang / Wu, Xinquan / Li, Liqiong / Wu, Wenyi

Open life sciences

2022 Volume 17, Issue 1, Page(s) 1116

Abstract: This corrects the article DOI: 10.1515/biol-2021-0099.]. ...

Abstract	[This corrects the article DOI: 10.1515/biol-2021-0099.].
Language	English
Publishing date	2022-09-08
Publishing country	Poland
Document type	Published Erratum
ZDB-ID	2817958-4
ISSN	2391-5412 ; 2391-5412
ISSN (online)	2391-5412
ISSN	2391-5412
DOI	10.1515/biol-2022-0083
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Article: ASF1B: A Possible Prognostic Marker, Therapeutic Target, and Predictor of Immunotherapy in Male Thyroid Carcinoma.

Qiu, Weigang / Wu, Xinquan / Shi, Haihong / Liu, Bingyang / Li, Liqiong / Wu, Wenyi / Lin, Jianqing

Frontiers in oncology

2022 Volume 12, Page(s) 678025

Abstract: Background: Thyroid carcinoma (TC) is the most common malignant endocrine tumor worldwide. Several studies have documented that male patients with TC have a higher rate of metastasis and disease recurrence than female patients. However, the mechanism ... ...

Abstract	Background: Thyroid carcinoma (TC) is the most common malignant endocrine tumor worldwide. Several studies have documented that male patients with TC have a higher rate of metastasis and disease recurrence than female patients. However, the mechanism underlying this observation is not completely clear. The goal of our research was to investigate the potential key candidate genes and pathways related to TC progression in male patients at the molecular level. Methods: A total of 320 samples were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Hub genes were screened out using weighted gene coexpression network analysis (WGCNA) and a protein-protein interaction (PPI) network analysis. Survival analysis was used to identify hub genes associated with disease-free survival (DFS) rates. Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression (ESTIMATE) data were used to assess the relationship between hub genes and immune cell infiltration. The molecular mechanism and biological functions of hub genes were explored using RT-qPCR, Western blot, Cell Counting Kit-8 Assay, flow cytometry, Transwell assays, and scratch assays. Results: Forty-seven hub genes were identified, and the survival analysis demonstrated that anti-silencing function 1B (ASF1B) was the sole independent risk factor for poor DFS in male TC patients. Possible associations between the results from the ESTIMATE analysis showed that the ASF1B expression level was related to the ESTIMATE score, immune score, and T-cell regulatory (Treg) infiltration level. Through Conclusions: Our results indicate that ASF1B can be considered a prognostic marker, therapeutic target, and predictor of immunotherapy response in male thyroid cancer patients. However, further in-depth studies are required to validate this finding.
Language	English
Publishing date	2022-01-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.678025
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Article ; Online: A two-microRNA signature predicts the progression of male thyroid cancer

Liu Bingyang / Shi Haihong / Qiu Weigang / Wu Xinquan / Li Liqiong / Wu Wenyi

Open Life Sciences, Vol 16, Iss 1, Pp 981-

2021 Volume 991

Abstract: In various cancers, microRNAs (miRNAs) are abnormally expressed, including thyroid cancer (TC). In recent years, the incidence of TC has increased annually around the world. Compared with female patients, male TC patients are more likely to have a ... ...

Abstract	In various cancers, microRNAs (miRNAs) are abnormally expressed, including thyroid cancer (TC). In recent years, the incidence of TC has increased annually around the world. Compared with female patients, male TC patients are more likely to have a postoperative recurrence and lymph node metastasis, and hence need second treatments. However, the molecular biological processes underlying this phenomenon are not understood. Therefore, we collected data on miRNA expression and clinical information of male TC patients from The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs were identified between male TC tissues and matched normal tissues. The Kaplan–Meier method, univariate and multivariate Cox regressions, and receiver operating characteristic curve analyses were performed to assess the association between miRNAs and the disease-free survival of male TC patients. Gene Ontology (GO) and the Kyoto Encyclopaedia of Gene and Genome (KEGG) enrichment analyses were then used to explore the function of miRNA target genes. Furthermore, we evaluated the ability of the miRNA biomarker to predict survival in female TC patients. As a result, a total of 118 differentially expressed miRNAs were identified, including 25 upregulated and 93 downregulated miRNAs. Among them, miR-451a and miR-16-1-3p were confirmed to be independent prognostic factors for the disease-free survival rate. The target genes of miR-451a and miR-16-1-3p were identified, and functional analysis showed that these genes were enriched in 25 Go and KEGG accessions, including cell signal transduction, motor adhesion, phagocytosis, regulation of transcription, cell proliferation, angiogenesis, etc. Neither miR-451a and miR-16-1-3p, nor a prediction model based on both miRNAs effectively predicted survival in female TC patients. In conclusion, both miR-451a and miR-16-1-3p may play important roles in the processes of male TC. The two-miRNA signature involving miR-1258 and miR-193a may serve as a novel prognostic biomarker for male TC patients.
Keywords	male thyroid cancer ; microrna signature ; tumour progression ; mir-451a ; mir-16-1-3p ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	De Gruyter
Document type	Article ; Online
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Article ; Online: Dosing recommendation of nirmatrelvir/ritonavir using an integrated population pharmacokinetic analysis.

Chan, Phylinda L S / Singh, Ravi Shankar P / Cox, Donna S / Shi, Haihong / Damle, Bharat / Nicholas, Timothy

CPT: pharmacometrics & systems pharmacology

2023 Volume 12, Issue 12, Page(s) 1897–1910

Abstract: Protease inhibitor nirmatrelvir coadministered with ritonavir as a pharmacokinetic enhancer (PAXLOVID™; Pfizer Inc) became the first orally bioavailable antiviral agent granted Emergency Use Authorization in the United States in patients ≥12 years old ... ...

Abstract	Protease inhibitor nirmatrelvir coadministered with ritonavir as a pharmacokinetic enhancer (PAXLOVID™; Pfizer Inc) became the first orally bioavailable antiviral agent granted Emergency Use Authorization in the United States in patients ≥12 years old with mild to moderate coronavirus disease 2019 (COVID-19). This population pharmacokinetic analysis used pooled plasma nirmatrelvir concentrations from eight completed phase I and II/III studies to characterize nirmatrelvir pharmacokinetics when coadministered with ritonavir in adults with/without COVID-19. Influence of covariates (e.g., formulation, dose, COVID-19) was examined using a stepwise forward selection (α = 0.05) and backward elimination (α = 0.001) approach. Simulations with 5000 subjects for each age and weight group and renal function category were performed to support dosing recommendations of nirmatrelvir/ritonavir for adults with COVID-19 and guide dose adjustments for specific patient populations (e.g., renal insufficiency, pediatrics). The final model was a two-compartment model with first-order absorption, including allometric scaling of body weight and dose-dependent absorption (power function on relative bioavailability). Nirmatrelvir clearance (CL) increased proportionally to body surface area-normalized creatinine CL (nCLCR) up to 70 ml/min/1.73 m
MeSH term(s)	Adult ; Humans ; Child ; Ritonavir ; Antiviral Agents ; Benzodiazepines ; COVID-19
Chemical Substances	Ritonavir (O3J8G9O825) ; Antiviral Agents ; Benzodiazepines (12794-10-4)
Language	English
Publishing date	2023-10-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2697010-7
ISSN	2163-8306 ; 2163-8306
ISSN (online)	2163-8306
ISSN	2163-8306
DOI	10.1002/psp4.13039
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Article ; Online: Effect of Hepatic Impairment on the Pharmacokinetics of Nirmatrelvir/Ritonavir, the First Oral Protease Inhibitor for the Treatment of COVID-19.

Singh, Ravi Shankar P / LaBadie, Robert R / Toussi, Sima S / Shi, Haihong / Berg, Jolene Kay / Neutel, Joel M / Aggarwal, Sudeepta

Journal of clinical pharmacology

2023 Volume 64, Issue 2, Page(s) 145–154

Abstract: Nirmatrelvir, a novel, potent, orally bioavailable severe acute respiratory syndrome coronavirus 2 main protease inhibitor, coadministered with ritonavir for pharmacokinetic (PK) enhancement is licensed for the treatment of mild to moderate COVID-19 in ... ...

Abstract	Nirmatrelvir, a novel, potent, orally bioavailable severe acute respiratory syndrome coronavirus 2 main protease inhibitor, coadministered with ritonavir for pharmacokinetic (PK) enhancement is licensed for the treatment of mild to moderate COVID-19 in individuals at increased risk of progression to severe disease. Cytochrome P450 3A4 is the primary metabolic enzyme responsible for nirmatrelvir metabolism; however, when cytochrome P450 3A4 is inhibited by ritonavir, nirmatrelvir is primarily excreted, unchanged, in urine. Because of intended use of nirmatrelvir among individuals with hepatic impairment, this Phase 1 study (NCT05005312) evaluated the effects of hepatic impairment on nirmatrelvir PK parameters to assess the potential need for any dose adjustments in this population. Participants with normal hepatic function or moderate hepatic impairment (n = 8 each) were administered a single 100-mg nirmatrelvir dose, with 100 mg of ritonavir administered 12 hours before, together with, and 12 and 24 hours after nirmatrelvir. Nirmatrelvir median plasma concentrations and systemic exposure measured by area under the plasma concentration-time curve from time zero extrapolated to infinite time and maximum observed plasma concentration values were comparable in both groups. Nirmatrelvir/ritonavir had an acceptable safety profile in both groups, and no clinically significant changes in laboratory measurements, vital signs, or electrocardiogram assessments were observed. Based on these results, no dose adjustment is deemed necessary in patients with moderate hepatic impairment and, by extension, in patients with mild hepatic impairment.
MeSH term(s)	Humans ; Ritonavir ; Protease Inhibitors/therapeutic use ; COVID-19 ; COVID-19 Drug Treatment ; Antiviral Agents/pharmacokinetics ; Liver Diseases/metabolism ; Cytochrome P-450 Enzyme System
Chemical Substances	Ritonavir (O3J8G9O825) ; Protease Inhibitors ; Antiviral Agents ; Cytochrome P-450 Enzyme System (9035-51-2)
Language	English
Publishing date	2023-10-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	188980-1
ISSN	1552-4604 ; 0091-2700 ; 0021-9754
ISSN (online)	1552-4604
ISSN	0091-2700 ; 0021-9754
DOI	10.1002/jcph.2353
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Article ; Online: High Expression of Serine Hydroxymethyltransferase 2 Indicates Poor Prognosis of Gastric Cancer Patients.

Shi, Haihong / Fang, Xiaoxu / Li, Yanfang / Zhang, Yingchun

Medical science monitor : international medical journal of experimental and clinical research

2019 Volume 25, Page(s) 7430–7438

Abstract: BACKGROUND Serine hydroxymethyltransferase (SHMT) is the enzyme that catalyzes the reversible conversion of serine to glycine and tetrahydrofolate-bound one-carbon unit. Upregulation of SHMT2 has been observed in a variety of cancers, but the expression ... ...

Abstract	BACKGROUND Serine hydroxymethyltransferase (SHMT) is the enzyme that catalyzes the reversible conversion of serine to glycine and tetrahydrofolate-bound one-carbon unit. Upregulation of SHMT2 has been observed in a variety of cancers, but the expression profile and clinical value of SHMT2 in gastric cancer (GC) are still unknown. MATERIAL AND METHODS In this study, SHMT2 expression was assessed in 130 patients with GC by immunohistochemistry (IHC). mRNA of SHMT2 in GC tissues and normal gastric epithelium was compared with qRT-PCR results. The correlations between SHMT2 and the clinicopathologic factors were analyzed with the chi-square test. Univariate analysis with Kaplan-Meier method was used to estimate the correlations between survival rate and clinicopathologic factors, including SHMT2. The independent prognostic biomarkers were confirmed by multivariate analysis using the Cox-regression hazard model. The function of SHMT2 in progression of GC was assessed by in vitro experiments. RESULTS The percentages of low and high expression of SHMT2 were 46.92% and 53.08%, respectively. SHMT2 mRNA in GC tissue was significantly higher than mRNA in the patient-paired adjacent tissues. In the clinical analysis, SHMT2 expression was notably associated with positive lymphatic invasion. High SHMT2 was also demonstrated to independently predict poor prognosis of GC. After silencing SHMT2, we proved that SHMT2 can promote proliferation and invasion of GC cells. CONCLUSIONS High SHMT2 promoted progression and was an independent prognostic biomarker of GC, suggesting that SHMT2 detection would be helpful for stratification of high-risk patients and thus directing personalized treatment.
MeSH term(s)	Adult ; Aged ; Biomarkers, Tumor/genetics ; China ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Glycine Hydroxymethyltransferase/genetics ; Glycine Hydroxymethyltransferase/physiology ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Stomach Neoplasms/genetics ; Stomach Neoplasms/physiopathology ; Survival Rate ; Transcriptome/genetics
Chemical Substances	Biomarkers, Tumor ; Glycine Hydroxymethyltransferase (EC 2.1.2.1) ; SHMT protein, human (EC 2.1.2.1)
Language	English
Publishing date	2019-10-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	1439041-3
ISSN	1643-3750 ; 1234-1010
ISSN (online)	1643-3750
ISSN	1234-1010
DOI	10.12659/MSM.917435
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Article ; Online: A Comprehensive Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Drug Interactions of Nirmatrelvir/Ritonavir.

Gerhart, Jacqueline / Cox, Donna S / Singh, Ravi Shankar P / Chan, Phylinda L S / Rao, Rohit / Allen, Richard / Shi, Haihong / Masters, Joanna C / Damle, Bharat

Clinical pharmacokinetics

2024 Volume 63, Issue 1, Page(s) 27–42

Abstract: Nirmatrelvir is a potent and selective inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease that is used as an oral antiviral coronavirus disease 2019 (COVID-19) treatment. To sustain unbound systemic trough ... ...

Abstract	Nirmatrelvir is a potent and selective inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease that is used as an oral antiviral coronavirus disease 2019 (COVID-19) treatment. To sustain unbound systemic trough concentrations above the antiviral in vitro 90% effective concentration value (EC
MeSH term(s)	Humans ; Ritonavir/pharmacology ; Ritonavir/therapeutic use ; Pandemics ; Drug Interactions ; COVID-19 ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Nitriles ; Drug Combinations ; Leucine ; Proline ; Lactams
Chemical Substances	nirmatrelvir and ritonavir drug combination ; Ritonavir (O3J8G9O825) ; Antiviral Agents ; Nitriles ; Drug Combinations ; Leucine (GMW67QNF9C) ; Proline (9DLQ4CIU6V) ; Lactams
Language	English
Publishing date	2024-01-04
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	197627-8
ISSN	1179-1926 ; 0312-5963
ISSN (online)	1179-1926
ISSN	0312-5963
DOI	10.1007/s40262-023-01339-y
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