Effect of Severe Renal Impairment on the Safety, Tolerability, and Pharmacokinetics of AMG 986
Introduction: AMG 986 is a first-in-class, novel apelin receptor small molecule agonist initially developed for the treatment of heart failure (HF). The safety and pharmacokinetics (PK) of AMG 986 in participants with renal impairment (RI) remains unknown.
Methods: This phase 1 study compared the safety and PK of AMG 986 200 mg in six participants with severe RI (estimated glomerular filtration rate [eGFR] 15-29 mL/min/1.73 m2) versus six participants with normal renal function (eGFR ≥ 90 mL/min/1.73 m2).
Results: Following a single oral dose of AMG 986 200 mg on day 1, the maximum observed concentration increased 1.41-fold (90% confidence interval [CI] 0.88-2.27) and the area under the curve from time zero to infinity increased 1.23-fold (90% CI 0.73-2.06) in participants with severe RI versus normal renal function. AMG 986 had an acceptable safety profile; all adverse events were mild in severity.
Conclusions: The results of this study support the enrollment of HF patients with RI to clinical trials of AMG 986 without the need for dose adjustments.
Approach to the patient with cholestasis and jaundice syndrome. Joint AMH, AMG, and AMEG scientific position statement
The term cholestasis refers to bile acid retention, whether within the hepatocyte or in the bile ducts of any caliber. Biochemically, it is defined by a level of alkaline phosphatase that is 1.67-times higher than the upper limit of normal. Cholestatic diseases can be associated with an inflammatory process of the liver that destroys hepatocytes (hepatitis), withjaundice (yellowing of the skin and mucus membranes, associated with elevated serum bilirubin levels), or with both, albeit the three concepts should not be considered synonymous. Cholestatic diseases can be classified as intrahepatic or extrahepatic, depending on their etiology.
Knowing the cause of the condition is important for choosing the adequate diagnostic studies and appropriate treatment in each case. A complete medical history, together with a thorough physical examination and basic initial studies, such as liver ultrasound and liver function tests, aid the clinician in deciding which path to follow, when managing the patient with cholestasis. In a joint effort, the Asociación Mexicana de Hepatología (AMH), the Asociación Mexicana de Gastroenterología (AMG) and the Asociación Mexicana de Endoscopia Gastrointestinal (AMEG) developed the first Mexican scientific position statement on said theme.
Wind energy and CO 2 emissions: AMG estimations for selected countries
This study analyzes the relationship between wind energy consumption, coal energy consumption, globalization, economic growth, and carbon emissions. Data from 37 countries for the period 2000-2019 are included in the analysis. To examine the long-term relationship between the variables, the AMG method, which considers the cross-section dependence and slope homogeneity, was used. According to the long-term coefficient estimates of the cointegrated variables, wind energy consumption has a statistically significant and negative effect on carbon emissions in the long run.
For example, a 1% increase in wind energy consumption reduces carbon emissions by 0.018%. On the other hand, the variable of globalization has a statistically significant and positive effect on carbon emissions in the long run. A 1% increase in globalization increases carbon emissions by 0.107%. These findings show the importance of wind energy consumption in reducing carbon emissions.
Muscle function assessed by the non-invasive method acoustic myography (AMG) in a Danish group of healthy adults
- Acoustic myography (AMG) is a non-invasive method to assess muscle function during daily activities. AMG has great scope for assessment of musculoskeletal problems. The aim of this study was to create an AMG data set for general clinical use and relate these findings to age and gender. 10 healthy subjects (5 men/5 women), in each decade from 20 to 69 years of age (n = 50), were assessed.
- Their clinical health was tested. AMG measurements were carried out on muscles involved in defined movements of the upper and lower extremities. Muscle performance was measured using efficiency (E-score) and fibre recruitment (temporal (T-score) and spatial (S-score) summation). AMG-measurements showed good reproducibility. In each age group, it was found that for all those daily living skills measured, there was no gender difference. A walking and stair climbing test revealed that both legs are used equally and in a balanced way in healthy subjects. Moreover, there was no change in this function with increasing age up to 69 years.
- However, a cycling test with loading revealed that in elderly subjects the coordination of muscle use is impaired compared to that of the younger adults. Finally, a flexion test of the arm revealed an age-related decrease in the efficiency/coordination of m.Biceps alone, and a keyboard writing test suggests no effect on m.Trapezius. This reference data set now illustrates the reproducibility and ease of use of acoustic myography in the clinic and provides a means of assessing individuals with musculoskeletal problems.
AMG-126737 |
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| T29969-10mg | TargetMol Chemicals | 10mg | Ask for price |
AMG-126737 |
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| T29969-1g | TargetMol Chemicals | 1g | Ask for price |
AMG-126737 |
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| T29969-1mg | TargetMol Chemicals | 1mg | Ask for price |
AMG-126737 |
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| T29969-50mg | TargetMol Chemicals | 50mg | Ask for price |
AMG-126737 |
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| T29969-5mg | TargetMol Chemicals | 5mg | Ask for price |
AMG-126737 |
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| MBS5779596-5mg | MyBiosource | 5(mg | 915 EUR |
AMG-126737 |
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| MBS5779596-5x5mg | MyBiosource | 5x5(mg | 3970 EUR |
AMG-3969 |
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| 530955 | MedKoo Biosciences | 5.0mg | 250 EUR |
AMG-9810 |
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| 524224 | MedKoo Biosciences | 50.0mg | 250 EUR |
AMG-9810 |
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| MBS131712-100mg | MyBiosource | 100mg | 1065 EUR |
AMG-9810 |
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| MBS131712-500mg | MyBiosource | 500mg | 2925 EUR |
AMG-3969 |
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| MBS131663-100mg | MyBiosource | 100mg | 1065 EUR |
AMG-3969 |
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| MBS131663-500mg | MyBiosource | 500mg | 2925 EUR |
AMG-3969 |
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| HY-12411 | MedChemExpress | 100mg | 3531.6 EUR |
AMG-1694 |
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| T14212-10mg | TargetMol Chemicals | 10mg | Ask for price |
AMG-1694 |
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| T14212-1g | TargetMol Chemicals | 1g | Ask for price |
AMG-1694 |
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| T14212-1mg | TargetMol Chemicals | 1mg | Ask for price |
AMG-1694 |
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| T14212-50mg | TargetMol Chemicals | 50mg | Ask for price |
AMG-1694 |
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| T14212-5mg | TargetMol Chemicals | 5mg | Ask for price |
AMG-7209 |
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| T23720-10mg | TargetMol Chemicals | 10mg | Ask for price |
AMG-7209 |
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| T23720-1g | TargetMol Chemicals | 1g | Ask for price |
AMG-7209 |
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| T23720-1mg | TargetMol Chemicals | 1mg | Ask for price |
Spotlight on Sotorasib (AMG 510) for KRAS G12C Positive Non-Small Cell Lung Cancer
Mutations in codon 12 of KRAS have been identified in 13% of non-small cell lung cancer patients. Developing targeted therapies against KRASG12C mutation has proven to be challenging due to the abundance of GTP in the cytoplasm, rapid hydrolysis of GTP, and difficulty designing small molecules to achieve sufficient concentration for KRAS inhibition. Based on promising results in both preclinical and clinical trials, sotorasib, a novel KRASG12C inhibitor, was given conditional approval by the FDA in May 2021.
The Phase I portion of the clinical trial produced 32% confirmed response with 56% of patients with stable disease. About 91.2% of patients who received the highest dose of 960mg daily achieved disease control. The Phase II portion, which used 960mg daily dosing resulted in 37.1% of patients with confirmed response and 80.6% of patients with disease control. Both phase I and phase II had similar progression-free survival, in 6.3 months and 6.8 months, respectively. In both phases, grade 4 adverse events occurred in only one patient.
The most common adverse events were elevations in LFTs, which down-trended upon dose reduction and steroid treatment. While the conditional approval of sotorasib was a major breakthrough for those patients harboring KRASG12C mutations, resistance mutations to sotorasib are increasingly common. Many proposals have been made to address this, such as the use of combination therapy for synthetic lethality, which are producing encouraging results. Here, we explore in further detail the development of sotorasib, its efficacy, mechanism of resistance, and strategies to overcome these resistances.