An Extension of Janmahasatian’s Fat-Free Mass Model for Universal Application Across Populations of Different Ethnicities

Sinha, Jaydeep; Al‐Sallami, Hesham S.; Duffull, Stephen B.

doi:10.1007/s40262-020-00883-1

Cited by 7 publications

(5 citation statements)

References 20 publications

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“…It should be noted that the population PK model, and the model for estimation of FFM were developed with data from predominantly Caucasian populations. Prescribers should use caution when applying these to patients of other ethnicities, where systematic differences in body composition can lead to bias in FFM estimation 32,33. The granular presentation of PTAs in this study allow prescribers to consider the potential effect of such bias, and adjust their dosing and monitoring decisions accordingly.The population PK model developed in this study has some limitations.…”

mentioning

confidence: 99%

Population pharmacokinetics of free flucloxacillin in patients treated with oral flucloxacillin plus probenecid

Drennan

Green

Gardiner

et al. 2021

Brit J Clinical Pharma

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Oral flucloxacillin may be coadministered with probenecid to reduce flucloxacillin clearance and increase attainment of pharmacokinetic-pharmacodynamic (PK/PD) targets. The aims of this study were to develop a population PK model of free flucloxacillin when administered orally with probenecid, and to identify optimal dosing regimens for this combination.Methods: We performed a prospective observational study of adults (45 participants) treated with oral flucloxacillin 1000 mg and probenecid 500 mg 8-hourly for proven or probable staphylococcal infections. Steady-state mid-dose-interval flucloxacillin measurements (45 concentrations) were combined with existing data from a crossover study of healthy participants receiving flucloxacillin with and without probenecid (11 participants, 363 concentrations). We developed a population pharmacokinetic model of free flucloxacillin concentrations within Monolix, and used Monte Carlo simulation to explore optimal dosing regimens to attain PK/PD targets proposed in the literature (free drug time above minimum inhibitory concentration).Results: Flucloxacillin disposition was best described by a 1-compartment model with a lag time and first-order absorption. Free flucloxacillin clearance depended on probenecid, allometrically-scaled fat free mass (FFM) and estimated glomerular filtration rate (eGFR). Predicted PK/PD target attainment was suboptimal with standard dosing regimens with flucloxacillin alone, but substantially improved in the presence of probenecid. Conclusion:The simulation results reported can be used to identify dose regimens that optimise flucloxacillin exposure according to eGFR and FFM. Patients with higher FFM and eGFR may require the addition of probenecid and 6-hourly dosing to achieve PK/PD targets. The regimen was well-tolerated, suggesting a potential for further evaluation in controlled clinical trials to establish efficacy.

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confidence: 99%

Population pharmacokinetics of free flucloxacillin in patients treated with oral flucloxacillin plus probenecid

Drennan

Green

Gardiner

et al. 2021

Brit J Clinical Pharma

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“…2 That FFM model has been extended down to children as young as 3 years of age 3 and also to include different ethnicities. 4 However, there is currently no continuous model predicting FFM from premature neonates to adults. Such a model would be useful to account for body composition in drug pharmacokinetics across the human age span.…”

Section: Introductionmentioning

confidence: 99%

“…Predictive equations for FFM have been described in adults 2 . That FFM model has been extended down to children as young as 3 years of age 3 and also to include different ethnicities 4 . However, there is currently no continuous model predicting FFM from premature neonates to adults.…”

Section: Introductionmentioning

confidence: 99%

Consistent methods for fat‐free mass, creatinine clearance, and glomerular filtration rate to describe renal function from neonates to adults

O’Hanlon

Holford

Sumpter

et al. 2023

CPT Pharmacom & Syst Pharma

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Quantifying the effect of kidney disease on glomerular filtration rate (GFR) is important when describing variability in the clearance of drugs eliminated by the kidney. We aimed to develop a continuous model for renal function (RF) from prematurity to adulthood based on consistent models for fat‐free mass (FFM), creatinine production rate (CPR), and GFR. A model for fractional FFM in premature neonates to adults was developed using pooled data from 4462 subjects and 2847 FFM observations. It was found that girls have an FFM higher than that predicted from adult women based on height, total body mass, and sex, and boys have an FFM lower than adult men until around the onset of puberty, when it approaches adult male values. Data from 108 subjects with measurements of serum creatinine (Scr) and GFR were used to construct a model for CPR. Creatinine clearance was predicted using a model for CPR (based on FFM, postmenstrual age, and sex) and Scr that avoids discontinuous predictions between neonates, children, and adults. Individual CPR may then be used with individual Scr to predict the estimated GFR (eGFR; eGFR = CPR/Scr). A previously published model for human GFR based on 1153 GFR observations in 923 subjects without known kidney disease was updated using the model for fractional FFM to predict individual size and age‐consistent values for the expected normal GFR (nGFR). Individual renal function was then calculated using RF = eGFR/nGFR.

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“…In the data analysis, the performance of the virtual PAWPER XL-MAC estimation of LBW was compared against the participants’ actual FFM (as measured using Dual Energy X-ray Absorptiometry (DXA), the gold standard for FFM measurement). In general, FFM and LBW are considered to be equivalent, although FFM may be slightly lower than LBW, as LBW includes the lipid mass in cell membranes, the central nervous system and bone marrow [ 5 , 19 ]. In this study, the term FFM is used to represent DXA-measured FFM, and the term LBW is used more generally, including for estimated values.…”

Section: Methodsmentioning

confidence: 99%

“…In general, lipophilic drugs should be dosed to total body weight (TBW) and hydrophilic drugs to ideal body weight (IBW) or lean body weight (LBW) [ 3 , 4 ]. Unfortunately, LBW cannot be measured in critically ill patients and can be difficult to estimate during a time-sensitive emergency and critical care [ 5 ]. The most common methods of estimating LBW, such as the Boer formula and the Janmahasatian formula, require complex mathematical calculations which can be time-consuming and prone to error, especially during emergencies [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Estimating Lean Body Weight in Adults With the PAWPER XL-MAC Tape Using Actual Measured Weight as an Input Variable

Wells¹,

Goldstein²

2022

Cureus

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IntroductionAccurate drug dose calculation in obese patients requires an estimation of lean body weight (LBW) for dosing hydrophilic medications. Inaccurate weight estimates during the management of critically ill obese adults may contribute to inaccurate drug doses and consequential poor outcomes. Existing methods of LBW estimation or measurement may be very difficult or impossible to use during emergency care. A point-ofcare model that could provide rapid, accurate estimates of LBW would, therefore, be of significant clinical value. MethodsA model was derived based using the adult version of the PAWPER XL-MAC tape. This derived model used recumbent length and measured total body weight (TBW) to estimate LBW. The derived model was used to generate LBW estimations in a random sample from National Health and Nutrition Examination Survey (NHANES) datasets (n=33,215). The benchmark outcome measure was to achieve >95% of LBW estimations within 20% of DXA-measured fat-free mass (P20>95%) and >70% of estimations within 10% of DXAmeasured fat-free mass (P10>70%). ResultsThe new model achieved a P20 of 99.7% and a P10 of 86.4% for LBW in the pooled sample and exceeded the minimum accuracy standards. This accuracy was maintained in both sexes, all ages, all ethnic groups, all lengths and in all habitus types. ConclusionsThe modified PAWPER XL-MAC model, using TBW as an input variable, proved to be an accurate method of LBW estimation. It could potentially have an important role in facilitating emergency drug dose calculations in critically ill or injured obese adult patients.

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An Extension of Janmahasatian’s Fat-Free Mass Model for Universal Application Across Populations of Different Ethnicities

Cited by 7 publications

References 20 publications

Population pharmacokinetics of free flucloxacillin in patients treated with oral flucloxacillin plus probenecid

Population pharmacokinetics of free flucloxacillin in patients treated with oral flucloxacillin plus probenecid

Consistent methods for fat‐free mass, creatinine clearance, and glomerular filtration rate to describe renal function from neonates to adults

Estimating Lean Body Weight in Adults With the PAWPER XL-MAC Tape Using Actual Measured Weight as an Input Variable

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