Dose translation from animal to human studies revisited

  title={Dose translation from animal to human studies revisited},
  author={Shannon R Reagan-Shaw and Minakshi Nihal and Nihal Ahmad},
  journal={The FASEB Journal},
  pages={659 - 661}
As new drugs are developed, it is essential to appropriately translate the drug dosage from one animal species to another. A misunderstanding appears to exist regarding the appropriate method for allomet‐ric dose translations, especially when starting new animal or clinical studies. The need for education regarding appropriate translation is evident from the media response regarding some recent studies where authors have shown that resveratrol, a compound found in grapes and red wine, improves… 

Dose Selection in Preclinical Studies: Cross-Species Dose Conversion

An overview of the main methods that can be used for selection and justification of animal doses in preclinical studies, e.g. cross-species dose conversion using body surface area scaling is provided, and situations when doses may be directly converted based on body weight are summarised.

Dose estimation, conversion and translation from animal to human and human to animal for clinical and animal studies.

To describe scientific methods for dose estimation and conversion for herbal, experimental and traditional drugs from animal to human and vice versa. Various databases were searched like FDA for

Translating dosages from animal models to human clinical trials—revisiting body surface area scaling

  • Otis L. BlanchardJ. Smoliga
  • Biology, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2015
It is demonstrated that recent recommendations for BSA are not appropriate for animal‐to‐human dosage conversions and pharmacokinetic data from resveratrol studies are used to demonstrate how confusion between the “human equivalent dose’ and “pharmacologically active dose” can lead to inappropriate dose recommendations.

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

The history of various models within allometry, including their advantages, disadvantages, and nuances from a clinical perspective are discussed, to promote a greater understanding of the role of allometric scaling in dose selection and provide an explanation for some of the apparent inconsistencies in translational research regarding resveratrol.

What is the best strategy for preclinical testing of botanicals? A critical perspective.

It is proposed that preclinical testing strategies of botanicals should start with the in vivo examination of extracts in relevant animal models to substantiate the ethnopharmacological/ethnopharmaceutical use, followed by bioguided fractionation processes using an adequate in vitro model, further followed by pharmacokinetic studies and final in vivo testing of isolated compounds.

How to Choose Drug Dosage for Human Experiments Based on Drug Dose Used on Animal Experiments: A Review

In insight to how to convert drug dose from animal studies to human trails, BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function.

Resveratrol in human cancer chemoprevention--choosing the 'right' dose.

There is now robust preclinical evidence to suggest that resveratrol possesses cancer chemopreventive properties. A series of clinical pilot studies has provided insights into its pharmacokinetics,

Improving the predictive power of xenograft and syngeneic anti-tumour studies using mice humanised for pathways of drug metabolism

A complex transgenic mouse model – 8HUM - is developed which faithfully replicates human Phase I drug metabolism (and its regulation), and which will generate more human-relevant data from fewer animals in a pre-clinical setting and reduce attrition in the clinic.

Starting Dose Calculation for Medicinal Plants in Animal Studies; Recommendation of a Simple and Reliable Method

A simple and reliable method of calculating the starting dose for animal studies based on Persian medicine, using the body surface area normalization method (BSA).

What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol

The published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources, and animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials.



Estimate of the safe starting dose in clinical trials for therapeutics in adult healthy volunteers

A strategy was proposed to determine the maximum recommended starting dose (MRSD) of any new drug or biological therapeutic that had been studied in animals, but was not pertinent to prophylactic vaccines or endogenous proteins used at physiologic concentrations.

The evaluation of anticancer drugs in dogs and monkeys for the prediction of qualitative toxicities in man

The usefulness of dogs and monkeys in predicting potential qualitative drug toxicity in man was examined retrospectively for twenty‐five anticancer compounds of diverse chemical and functional

Chemotherapy dosing part I: scientific basis for current practice and use of body surface area.

  • S. KaestnerG. Sewell
  • Medicine, Biology
    Clinical oncology (Royal College of Radiologists (Great Britain))
  • 2007

Body Surface Area as a Determinant of Pharmacokinetics and Drug Dosing

Body surface area was introduced intomedical oncology in order to derive a safestarting dose for phase I studies ofanticancer drugs from preclinical animaltoxicology data, but future clinicaltrials of new agents should not presumethat dosing based on BSA reduces interpatient variability.

Role of body surface area in dosing of investigational anticancer agents in adults, 1991-2001.

It is concluded that body surface area should not be used to determine starting doses of investigational agents in future phase I studies and alternate dosing strategies should be evaluated.

How to calculate the dose of chemotherapy

  • H. Gurney
  • Medicine
    British Journal of Cancer
  • 2002
Twelve rules for dose calculation of chemotherapy are given and consideration should be given to using fixed dose guidelines independent of body surface area and based on drug elimination capability, both as a starting dose and for dose adjustment, which may have accuracy, safety and financial advantages.

Resveratrol improves health and survival of mice on a high-calorie diet

It is shown that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice onA standard diet and significantly increases their survival and point to new approaches for treating obesity-related disorders and diseases of ageing.

Biological effects of resveratrol.

The use of body surface area as a criterion of drug dosage in cancer chemotherapy.

  • D. Pinkel
  • Biology, Medicine
    Cancer research
  • 1958
The rationale for the use of body surface area as the criterion of dosage in anticancer chemotherapy has been outlined and it is suggested that cancer chemotherapists consider the applicability of body surfaces as a criterion of drug dosage in their laboratory and clinical studies.

Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer

A positive association between metabolic intensity (kJ daily food assimilation expressed as g/body mass) and lifespan, but no relationships of lifespan to body mass, fat mass or lean body mass is found.