Allometric scaling models: history, use, and misuse in translating resveratrol from basic science to human clinical applications

Smoliga, James M.; Blanchard, Otis L.

doi:10.31989/ffhd.v7i5.345

Cited by 7 publications

(5 citation statements)

References 37 publications

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“…Based on doses in mg/kg and in mg/m 2 , most of the animal doses exceeded the recommended 800 mg bidaily dose in humans. Body-surface-area-based scaling enables the conversion of drug doses from one species to another, and is often used for the calculation of the human dose when a drug proceeds from animal studies and the preclinical development phase to the first trials in humans, but it requires similar pharmacokinetics and pharmacodynamics in humans and the animal species used [57][58][59]. If these requirements are not met, the method may underestimate the effective dose in humans [57].…”

Section: Dose Levels Of Molnupiravirmentioning

confidence: 99%

Molnupiravir Revisited—Critical Assessment of Studies in Animal Models of COVID-19

Rasmussen,

Hansen

2023

Viruses

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Molnupiravir, a prodrug known for its broad antiviral activity, has demonstrated efficacy in animal models of COVID-19, prompting clinical trials, in which initial results indicated a significant effect against the disease. However, subsequent clinical studies did not confirm these findings, leading to the refusal of molnupiravir for permanent market authorization in many countries. This report critically assessed 22 studies published in 18 reports that investigated the efficacy of molnupiravir in animal models of COVID-19, with the purpose of determining how well the design of these models informed human studies. We found that the administered doses of molnupiravir in most studies involving animal COVID-19 models were disproportionately higher than the dose recommended for human use. Specifically, when adjusted for body surface area, over half of the doses of molnupiravir used in the animal studies exceeded twice the human dose. Direct comparison of reported drug exposure across species after oral administration of molnupiravir indicated that the antiviral efficacy of the dose recommended for human use was underestimated in some animal models and overestimated in others. Frequently, molnupiravir was given prophylactically or shortly after SARS-CoV-2 inoculation in these models, in contrast to clinical trials where such timing is not consistently achieved. Furthermore, the recommended five-day treatment duration for humans was exceeded in several animal studies. Collectively, we suggest that design elements in the animal studies under examination contributed to a preference favoring molnupiravir, and thus inflated expectations for its efficacy against COVID-19. Addressing these elements may offer strategies to enhance the clinical efficacy of molnupiravir for the treatment of COVID-19. Such strategies include dose increment, early treatment initiation, administration by inhalation, and use of the drug in antiviral combination therapy.

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Section: Dose Levels Of Molnupiravirmentioning

confidence: 99%

Molnupiravir Revisited—Critical Assessment of Studies in Animal Models of COVID-19

Rasmussen,

Hansen

2023

Viruses

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“…Allometric scaling is a method that is often used to calculate the appropriate dose for humans [21,22].…”

Section: Food Trialmentioning

confidence: 99%

Establishment of Dosage of Bioactive Compounds in Functional Food Products

Martirosyan¹,

Sanchez

2022

FFS

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As the prevalence of chronic diseases has increased in the United States there has also been an increase in the need for products that can help prevent, manage, or treat diseases. Functional food products can do this through components within them called bioactive compounds. These compounds can provide multiple health benefits that act on biomarkers of disease. However, there is not a set definition for functional foods, making it hard to classify and regulate them. The Functional Food Center has proposed a definition for functional food as well as a multi-step process for their development. As part of this process a bioactive compound is identified within a functional food product. To understand more about the safety and efficacy of this bioactive compound, an appropriate dose must be established. To find this dose, clinical research is conducted. In preclinical research animal subjects are used to identify the critical amount of a bioactive compound. Researchers also test for safety concerns and adverse effects from the product. After this, clinical trials are performed on human subjects to determine the efficacy of the functional food product. However, these trials are different from trials done on drugs. The quantum theory of functional food science can find the critical amount of a bioactive compound needed to create a chain reaction that leads to the claimed health benefits. This can also help researchers discover possible toxicities of bioactive compounds in doses above the critical amount. The use of quantum mechanics in the food industry could also allow for control of physical characteristics of functional food products as well as bioavailability of bioactive compounds within these products using nanotechnology. However, more research is needed to understand the safety of this technology. Keywords: functional food products, bioactive compounds, dosage, pre-clinical studies, clinical studies, quantum theory of functional food sciences, quantum mechanics

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“…Although using animal subjects allows researchers to understand complex organisms better without having to use human subjects, it is not clear what the correct way to convert the dose from an animal subject to a human subject should be, which could lead to inappropriate amounts of a BC being used on human subjects [7]. There are different methods that have been used to make these conversions, including allometric scaling which, if used correctly, can effectively convert the appropriate dosage from animals to humans that should be used [8]. This technique is based on correlations between species that have similar characteristics and uses metabolic rates and body size to predict the appropriate dose for humans [8].…”

Section: Quantum Theory Of Functional Food Sciencementioning

confidence: 99%

“…There are different methods that have been used to make these conversions, including allometric scaling which, if used correctly, can effectively convert the appropriate dosage from animals to humans that should be used [8]. This technique is based on correlations between species that have similar characteristics and uses metabolic rates and body size to predict the appropriate dose for humans [8].…”

Section: Quantum Theory Of Functional Food Sciencementioning

confidence: 99%

Quantum and Tempus Theories of Functional Food Science: Establishment of dosage and time of consumption of functional food products

Martirosyan¹,

Sanchez

2022

FFS

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Over the years the United States has seen an increase in the prevalence of chronic diseases. For that reason, there has also been an increased need in products that can prevent or manage symptoms of disease. Functional food products are food products that contain bioactive compounds that have been shown to produce beneficial effects that increase health. The Functional Food Center has previously a 16-step process to develop functional food products and bring them to the market. As part of this process, researchers should establish the appropriate dosage of a bioactive compound at which the product can be consumed safely, and it can effectively improve health parameters. Previously, we suggested that Quantum theory of functional food science could be useful for finding the critical amount at which a bioactive compound will cause enough chain reactions to influence health and biomarkers of disease. In this paper, we propose that a new step be added to the 16-step process making the total steps to bring a functional food product to the market 17. This new step should occur after establishing the appropriate dose and should focus on establishing the appropriate time of consumption using the Tempus theory of functional food science. The word Tempus comes from the latin word for time. Similar to dosage, time of consumption can impact the effectiveness of a bioactive compound, which is why this new step is important. Recent studies on diabetic patients have applied the Quantum and Tempus theories of functional food science to determine the appropriate range of dosage and time of consumption at which squalene, which is a bioactive compound belonging to the triterpene class, can improve parameters of health in diabetics. The studies found that consumption of squalene improves parameters of health in diabetic patients, however higher doses produced the effects in less time than lower doses. Although the studies were able to provide more information about the appropriate dose and time range for consuming the bioactive compound in that population, more research is needed to find the exact ranges.Keywords: functional food product, bioactive compound, dosage, time, quantum theory of functional food science, tempus theory of functional food science

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Allometric scaling models: history, use, and misuse in translating resveratrol from basic science to human clinical applications

Cited by 7 publications

References 37 publications

Molnupiravir Revisited—Critical Assessment of Studies in Animal Models of COVID-19

Molnupiravir Revisited—Critical Assessment of Studies in Animal Models of COVID-19

Establishment of Dosage of Bioactive Compounds in Functional Food Products

Quantum and Tempus Theories of Functional Food Science: Establishment of dosage and time of consumption of functional food products

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