Dataset Information

Normal fat mass cannot be reliably estimated in typical pharmacokinetic studies.

ABSTRACT:

Purpose

An influential covariate for pharmacokinetics is (body) size. Recently, the method of estimation of normal fat mass (NFM) has been advocated. Here, the relative contribution of fat mass, estimated as a fraction fat (Ffat), is used to explain differences in pharmacokinetic parameters. This concept is more and more applied. However, it remains unclear whether NFM can be reliably estimated in these typical studies.

Methods

We performed an evaluation of the reliability of NFM estimation in a typical study size (n = 30), otherwise best-case scenario, by means of a pharmacokinetic simulation study. Several values of Ffat were investigated.

Results

In a typical pharmacokinetic study, high imprecision was observed for NFM parameter estimates over a range of scenarios. For example, in a scenario where the true value of Ffat on clearance was 0.5, we found a 95% confidence interval of - 0.1 to 2.1, demonstrating a low precision. The implications for practice are that one could conclude that fat-free mass best describes the relationship of the pharmacokinetics with body size, while the true relationship was between fat-free mass and total body weight. Consequently, this could lead to incorrect extrapolation of pharmacokinetics to extreme body sizes.

Conclusion

In typical pharmacokinetic studies, NFM should be used with caution because the Ffat estimates have low precision. The estimation of Ffat should always be preceded by careful study design evaluation before planning a study, to ensure that the design and sample size is sufficient to apply this potentially useful methodology.

SUBMITTER: Wasmann RE

PROVIDER: S-EPMC8032617 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Normal fat mass cannot be reliably estimated in typical pharmacokinetic studies.

Wasmann Roeland E RE Svensson Elin M EM Schalkwijk Stein J SJ Brüggemann Roger J RJ Ter Heine Rob R

European journal of clinical pharmacology 20201118 5

<h4>Purpose</h4>An influential covariate for pharmacokinetics is (body) size. Recently, the method of estimation of normal fat mass (NFM) has been advocated. Here, the relative contribution of fat mass, estimated as a fraction fat (Ffat), is used to explain differences in pharmacokinetic parameters. This concept is more and more applied. However, it remains unclear whether NFM can be reliably estimated in these typical studies.<h4>Methods</h4>We performed an evaluation of the reliability of NFM ...[more]

PMID: 33205282

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Project description:Background/objectivesWe aimed to investigate the association of waist circumference (WC) with body composition among individuals with a normal body mass index (BMI) to distinguish muscle and fat mass, as both affect health differently.Subjects/methodsWe analyzed dual-energy X-ray absorptiometry data (derived from the Korean National Health and Nutrition Survey, which includes information on fat and lean mass) of 7,493 adults with a normal BMI. Subjects were categorized into four groups of increasing WC. The fourth group was defined as being centrally obese. Each number of subjects are as follows: 1,870, 695, 231, and 39 among men and 3,054, 1,100, 406, and 98 among women. We conducted a sex-stratified linear regression analysis of body composition according to WC group after adjustments for covariates.ResultsWe observed a positive association of body fat with increasing WC in both men and women (all P for trend: < 0.001). The adjusted mean values for percent body fat with 95% confidence intervals (CIs) according to the four WC groups in ascending order were 17.8 (17.5-18.3), 21.0 (20.6-21.5), 22.1 (21.5-22.8), and 25.1 (24.2-26.1) in men and 29.7 (29.4-30.0), 32.0 (31.6-32.3), 32.9 (32.4-33.4), and 34.7 (33.2-36.1) in women. However, there was an inverted J-shaped association between muscle mass and WC. The fourth group had a higher percent body fat and lower muscle mass than other groups. The adjusted mean values for appendicular skeletal muscle mass index (kg/m2) with 95% CIs according to the four WC groups in ascending order were 7.55 (7.51-7.59), 7.62 (7.56-7.68), 7.65 (7.56-7.74), and 7.22 (7.04-7.41) in men and 5.83 (5.80-5.85), 5.96 (5.92-6.00), 6.03 (5.96-6.10), and 5.88 (5.73-6.03).ConclusionsThere was a positive association between body fat and WC among individuals with normal BMI; conversely there was an inverted J-shaped association between lean body mass and WC. Our findings support the WC measurement should be included in obesity evaluations for adults with a normal BMI.

Dataset Information

Normal fat mass cannot be reliably estimated in typical pharmacokinetic studies.

Purpose

Methods

Results

Conclusion

Publications

Normal fat mass cannot be reliably estimated in typical pharmacokinetic studies.

Similar Datasets

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