A global examination of allometric scaling for predicting human drug clearance and the prediction of large vertical allometry**This work was presented at the American Association of Pharmaceutical Scientists Annual meeting, Salt Lake City, USA, Oct. 26, 2003.

Tang, Huadong; Mayersohn, Michael

doi:10.1002/jps.20481

Cited by 81 publications

(6 citation statements)

References 123 publications

(22 reference statements)

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“…Mordenti and colleagues reported exponents that ranged from 0.65 to 0.84 for clearance and from 0.84 to 1.02 for V ss for five human proteins (19). Broader ranges for the allometric exponent for systemic clearance were also reported by Mahmood (0.64–1.29 for 15 proteins) (20) and Tang and Mayersohn (0.56–1.06 for 10 proteins) (21). Lave and colleagues found allometric exponents for clearance and V ss of 0.71 and 0.94 for human IFN-α.…”

Section: Discussionsupporting

confidence: 61%

Interspecies Scaling of Receptor-Mediated Pharmacokinetics and Pharmacodynamics of Type I Interferons

et al. 2010

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Purpose To develop an integrated mechanism-based modeling approach for the interspecies scaling of pharmacokinetic (PK) and pharmacodynamic (PD) properties of type I interferons (IFNs) that exhibit target-mediated drug disposition (TMDD). Methods PK and PD profiles of human IFN-β1a, IFN-β1b, and IFN-α2a in humans, monkeys, rats, and mice from nine studies were extracted from the literature by digitization. Concentration-time profiles from different species were fitted simultaneously using various allometric relationships to scale model-specific parameters. Results PK/PD profiles of IFN-β1a in humans and monkeys were successfully characterized by utilizing the same rate constant parameters and scaling the volume of the central compartment to body weight using an allometric exponent of 1. Concentration and effect profiles of other IFNs were also well described by changing only the affinity of the drug to its receptor. PK profiles in rodents were simulated using an allometric exponent of −0.25 for the first-order elimination rate constant, and no receptor-binding was included given the lack of cross-reactivity. Conclusions An integrated TMDD PK/PD model was successfully combined with classic allometric scaling techniques and showed good predictive performance. Several parameters obtained from one IFN can be effectively shared to predict the kinetic behavior of other IFN subtypes.

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Section: Discussionsupporting

confidence: 61%

Interspecies Scaling of Receptor-Mediated Pharmacokinetics and Pharmacodynamics of Type I Interferons

et al. 2010

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“…The value of the exponent b is typically <1, 16,78 meaning that CL increases slower than weight, i.e., heavier animals have relatively lower CL (per unit of body weight), compared to smaller animals. Sometimes, however, the exponent is estimated at >1, 62,79 indicating that this method is not the most appropriate. To address this, but still use simple allometry, mathematical corrections to decrease and thus improve the mAb human CL prediction were suggested.…”

Section: Simple Allometrymentioning

confidence: 99%

Allometric scaling of therapeutic monoclonal antibodies in preclinical and clinical settings

Germovsek

Jin

Giragossian

2021

mAbs

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Constant technological advancement enabled the production of therapeutic monoclonal antibodies (mAbs) and will continue to contribute to their rapid expansion. Compared to small-molecule drugs, mAbs have favorable characteristics, but also more complex pharmacokinetics (PK), e.g., target-mediated nonlinear elimination and recycling by neonatal Fc-receptor. This review briefly discusses mAb biology, similarities and differences in PK processes across species and within human, and provides a detailed overview of allometric scaling approaches for translating mAb PK from preclinical species to human and extrapolating from adults to children. The approaches described here will remain vital in mAb drug development, although more data are needed, for example, from very young patients and mAbs with nonlinear PK, to allow for more confident conclusions and contribute to further growth of this field. Improving mAb PK predictions will facilitate better planning of (pediatric) clinical studies and enable progression toward the ultimate goal of expediting drug development.

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“…Diazepam is in fact a good example of where microdosing could be useful, as its clearance is significantly over-predicted by allometric scaling. Diazepam, along with certain other drugs such as warfarin, reboxetine and tamsulosin, are classed as having “a large verti cal allometry” where clearance is over-predicted, by over 3000% in the case of diazepam [49]. These magnitudes of errors have not been seen thus far with microdosing, even in the case of warfarin where target-mediated disposition is a demonstrated mechanism on non-linearity.…”

Section: The Utility Of Microdosingmentioning

confidence: 99%

“…[49] ‡ The dose range is given between a microdose and a therapeutic dose in the study cited or for a typical therapeutic dose if compared to the literature (see comment column). § Summarised mean parameters. ¶ Data for zidovudine were ambiguous in that one publication reported scalable pharmacokinetics in PBMCs [65], whilst the other reported non-linear pharmacokinetics [66]. Since the plasma pharmacokinetics for both papers reported saleable pharmacokinetics, zidovudine has been included with those drugs where microdosing was predictive within a factor of 2.…”

Section: Article Highlightsmentioning

confidence: 99%

Microdosing and drug development: past, present and future

Lappin

Noveck²,

Burt

2013

Expert Opinion on Drug Metabolism & Toxicology

115

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Introduction Microdosing is an approach to early drug development where exploratory pharmacokinetic data are acquired in humans using inherently safe sub-pharmacologic doses of drug. The first publication of microdose data was 10 years ago and this review comprehensively explores the microdose concept from conception, over the past decade, up until the current date. Areas covered The authors define and distinguish the concept of microdosing from similar approaches. The authors review the ability of microdosing to provide exploratory pharmacokinetics (concentration-time data) but exclude microdosing using positron emission tomography. The article provides a comprehensive review of data within the peer-reviewed literature as well as the latest applications and a look into the future, towards where microdosing may be headed. Expert opinion Evidence so far suggests that microdosing may be a better predictive tool of human pharmacokinetics than alternative methods and combination with physiologically based modelling may lead to much more reliable predictions in the future. The concept has also been applied to drug-drug interactions, polymorphism and assessing drug concentrations over time at its site of action. Microdosing may yet have more to offer in unanticipated directions and provide benefits that have not been fully realised to date.

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A global examination of allometric scaling for predicting human drug clearance and the prediction of large vertical allometry**This work was presented at the American Association of Pharmaceutical Scientists Annual meeting, Salt Lake City, USA, Oct. 26, 2003.

Cited by 81 publications

References 123 publications

Interspecies Scaling of Receptor-Mediated Pharmacokinetics and Pharmacodynamics of Type I Interferons

Interspecies Scaling of Receptor-Mediated Pharmacokinetics and Pharmacodynamics of Type I Interferons

Allometric scaling of therapeutic monoclonal antibodies in preclinical and clinical settings

Microdosing and drug development: past, present and future

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