Skip to main content
Top
Published in: Clinical Pharmacokinetics 10/2005

01-10-2005 | Original Research Article

Quantification of Lean Bodyweight

Authors: Sarayut Janmahasatian, Dr Stephen B. Duffull, Susan Ash, Leigh C. Ward, Nuala M. Byrne, Bruce Green

Published in: Clinical Pharmacokinetics | Issue 10/2005

Login to get access

Abstract

Background: Lean bodyweight (LBW) has been recommended for scaling drug doses. However, the current methods for predicting LBW are inconsistent at extremes of size and could be misleading with respect to interpreting weight-based regimens.
Objective: The objective of the present study was to develop a semi-mechanistic model to predict fat-free mass (FFM) from subject characteristics in a population that includes extremes of size. FFM is considered to closely approximate LBW. There are several reference methods for assessing FFM, whereas there are no reference standards for LBW.
Patients and methods: A total of 373 patients (168 male, 205 female) were included in the study. These data arose from two populations. Population A (index dataset) contained anthropometric characteristics, FFM estimated by dual-energy x-ray absorptiometry (DXA — a reference method) and bioelectrical impedance analysis (BIA) data. Population B (test dataset) contained the same anthropometric measures and FFM data as population A, but excluded BIA data. The patients in population A had a wide range of age (18–82 years), bodyweight (40.7–216.5kg) and BMI values (17.1–69.9 kg/m2). Patients in population B had BMI values of 18.7–38.4 kg/m2. A two-stage semi-mechanistic model to predict FFM was developed from the demographics from population A. For stage 1 a model was developed to predict impedance and for stage 2 a model that incorporated predicted impedance was used to predict FFM. These two models were combined to provide an overall model to predict FFM from patient characteristics. The developed model for FFM was externally evaluated by predicting into population B.
Results: The semi-mechanistic model to predict impedance incorporated sex, height and bodyweight. The developed model provides a good predictor of impedance for both males and females (r2 = 0.78, mean error [ME] = 2.30 × 10−3, root mean square error [RMSE] = 51.56 [approximately 10% of mean]). The final model for FFM incorporated sex, height and bodyweight. The developed model for FFM provided good predictive performance for both males and females (r2 = 0.93, ME = −0.77, RMSE = 3.33 [approximately 6% of mean]). In addition, the model accurately predicted the FFM of subjects in population B (r2 = 0.85, ME = −0.04, RMSE = 4.39 [approximately 7% of mean]).
Conclusions: A semi-mechanistic model has been developed to predict FFM (and therefore LBW) from easily accessible patient characteristics. This model has been prospectively evaluated and shown to have good predictive performance.
Literature
1.
go back to reference Kopelman PG. Obesity as a medical problem. Nature 2000; 404(6778): 635–43PubMed Kopelman PG. Obesity as a medical problem. Nature 2000; 404(6778): 635–43PubMed
2.
go back to reference Green B, Duffull SB. What is the best size descriptor to use for pharmacokinetic studies in the obese? Br J Clin Pharmacol 2004; 58(2): 119–33PubMedCrossRef Green B, Duffull SB. What is the best size descriptor to use for pharmacokinetic studies in the obese? Br J Clin Pharmacol 2004; 58(2): 119–33PubMedCrossRef
3.
go back to reference Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet 2000; 39(3): 215–31PubMedCrossRef Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet 2000; 39(3): 215–31PubMedCrossRef
4.
go back to reference Green B, Duffull SB. Development of a dosing strategy for enoxaparin in obese patients. Br J Clin Pharmacol 2002; 56: 96–103CrossRef Green B, Duffull SB. Development of a dosing strategy for enoxaparin in obese patients. Br J Clin Pharmacol 2002; 56: 96–103CrossRef
5.
go back to reference Sarubbi Jr FA, Hull JH. Amikacin serum concentrations: prediction of levels and dosage guidelines. Ann Intern Med 1978; 89(5 Pt 1): 612–8PubMed Sarubbi Jr FA, Hull JH. Amikacin serum concentrations: prediction of levels and dosage guidelines. Ann Intern Med 1978; 89(5 Pt 1): 612–8PubMed
6.
go back to reference Wulfsohn NL. Succinylcholine dosage based on lean body mass. Can Anaesth Soc J 1972; 19(4): 360–72PubMedCrossRef Wulfsohn NL. Succinylcholine dosage based on lean body mass. Can Anaesth Soc J 1972; 19(4): 360–72PubMedCrossRef
7.
go back to reference Green B, Duffull SB. Caution when lean body weight is used as a size descriptor for obese subjects. Clin Pharmacol Ther 2002; 72(6): 743–4PubMedCrossRef Green B, Duffull SB. Caution when lean body weight is used as a size descriptor for obese subjects. Clin Pharmacol Ther 2002; 72(6): 743–4PubMedCrossRef
8.
go back to reference Morgan DJ, Bray KM. Lean body mass as a predictor of drug dosage: implications for drug therapy. Clin Pharmacokinet 1994; 26(4): 292–307PubMedCrossRef Morgan DJ, Bray KM. Lean body mass as a predictor of drug dosage: implications for drug therapy. Clin Pharmacokinet 1994; 26(4): 292–307PubMedCrossRef
9.
go back to reference Duffull SB, Dooley MJ, Green B, et al. A standard weight descriptor for dose adjustment in the obese patient: what is the best size descriptor to use for pharmacokinetic studies in the obese? Clin Pharmacokinet 2004; 43(15): 1167–78PubMedCrossRef Duffull SB, Dooley MJ, Green B, et al. A standard weight descriptor for dose adjustment in the obese patient: what is the best size descriptor to use for pharmacokinetic studies in the obese? Clin Pharmacokinet 2004; 43(15): 1167–78PubMedCrossRef
10.
go back to reference Roche AF, Heymsfield SB, Lohman TG, editors. Human body composition. Champaign (IL): Human Kinetics, 1996 Roche AF, Heymsfield SB, Lohman TG, editors. Human body composition. Champaign (IL): Human Kinetics, 1996
11.
go back to reference Pi-Sunyer FX. Obesity: criteria and classification. Proc Nutr Soc 2000; 59(4): 505–9PubMed Pi-Sunyer FX. Obesity: criteria and classification. Proc Nutr Soc 2000; 59(4): 505–9PubMed
12.
go back to reference Bioelectrical impedance analysis in body composition measurement. Bethesda (MD): National Institutes of Health, Public Health Service, 1994 Dec 12–14 Bioelectrical impedance analysis in body composition measurement. Bethesda (MD): National Institutes of Health, Public Health Service, 1994 Dec 12–14
14.
go back to reference Ellis KJ. Human body composition: in vivo methods. Physiol Rev 2000; 80(2): 649–80PubMed Ellis KJ. Human body composition: in vivo methods. Physiol Rev 2000; 80(2): 649–80PubMed
15.
go back to reference Stewart AD, Hannan WJ. Prediction of fat and fat-free mass in male athletes using dual x-ray absorptiometry as the reference method. J Sports Sci 2000; 18(4): 263–74PubMedCrossRef Stewart AD, Hannan WJ. Prediction of fat and fat-free mass in male athletes using dual x-ray absorptiometry as the reference method. J Sports Sci 2000; 18(4): 263–74PubMedCrossRef
16.
go back to reference Pietrobelli A, Formica C, Wang Z, et al. Dual-energy x-ray absorptiometry body composition model: review of physical concepts. Am J Physiol 1996; 271(6 Pt 1): E941–51PubMed Pietrobelli A, Formica C, Wang Z, et al. Dual-energy x-ray absorptiometry body composition model: review of physical concepts. Am J Physiol 1996; 271(6 Pt 1): E941–51PubMed
17.
go back to reference Blake G, Fogelman I. Technical principles of dual energy x-ray absorptiometry. Semin Nucl Med 1997; 37: 210–28 Blake G, Fogelman I. Technical principles of dual energy x-ray absorptiometry. Semin Nucl Med 1997; 37: 210–28
18.
go back to reference Heymsfield SB, Smith R, Aulet M, et al. Appendicular skeletal muscle mass: measurement by dual-photon absorptiometry. Am J Clin Nutr 1990; 52(2): 214–8PubMed Heymsfield SB, Smith R, Aulet M, et al. Appendicular skeletal muscle mass: measurement by dual-photon absorptiometry. Am J Clin Nutr 1990; 52(2): 214–8PubMed
19.
go back to reference Beal SL, Sheiner LB. NONMEM user’s guide (Pt I). San Francisco (CA): University of California, 1992 Beal SL, Sheiner LB. NONMEM user’s guide (Pt I). San Francisco (CA): University of California, 1992
20.
go back to reference Sheiner LB, Beal SL. Some suggestions for measuring predictive performance. J Pharmacokinet Biopharm 1981; 9(4): 503–12PubMed Sheiner LB, Beal SL. Some suggestions for measuring predictive performance. J Pharmacokinet Biopharm 1981; 9(4): 503–12PubMed
21.
go back to reference Akaike H. A new look at the statistical model identification. IEEE Trans Automat Contr 1974; 19: 716–23CrossRef Akaike H. A new look at the statistical model identification. IEEE Trans Automat Contr 1974; 19: 716–23CrossRef
22.
go back to reference Lukaski HC, Johnson PE, Bolonchuk WW, et al. Assessment of fat-free mass using bioelectrical impedance measurements of the human body. Am J Clin Nutr 1985; 41(4): 810–7PubMed Lukaski HC, Johnson PE, Bolonchuk WW, et al. Assessment of fat-free mass using bioelectrical impedance measurements of the human body. Am J Clin Nutr 1985; 41(4): 810–7PubMed
23.
go back to reference Lohman TG. Advances in body composition assessment. Champaign (IL): Human Kinetics, 1992 Lohman TG. Advances in body composition assessment. Champaign (IL): Human Kinetics, 1992
24.
go back to reference James W. Research on obesity. London: Her Majesty’s Stationery Office, 1976 James W. Research on obesity. London: Her Majesty’s Stationery Office, 1976
25.
go back to reference Womersley J, Boddy K, King PC, et al. A comparison of the fat-free mass of young adults estimated by anthropometry, body density and total body potassium content. Clin Sci 1972; 43(3): 469–75PubMed Womersley J, Boddy K, King PC, et al. A comparison of the fat-free mass of young adults estimated by anthropometry, body density and total body potassium content. Clin Sci 1972; 43(3): 469–75PubMed
26.
go back to reference Hume R, Weyers E. Relationship between total body water and surface area in normal and obese subjects. J Clin Pathol 1971; 24(3): 234–8PubMedCrossRef Hume R, Weyers E. Relationship between total body water and surface area in normal and obese subjects. J Clin Pathol 1971; 24(3): 234–8PubMedCrossRef
27.
go back to reference Boddy K, King PC, Hume R, et al. The relation of total body potassium to height, weight, and age in normal adults. J Clin Pathol 1972; 25(6): 512–7PubMedCrossRef Boddy K, King PC, Hume R, et al. The relation of total body potassium to height, weight, and age in normal adults. J Clin Pathol 1972; 25(6): 512–7PubMedCrossRef
28.
go back to reference Anon. Obesity: preventing and managing the global epidemic. Report of a WHO consultation on obesity. Geneva: World Health Organization, 1997 Jun 3–5 Anon. Obesity: preventing and managing the global epidemic. Report of a WHO consultation on obesity. Geneva: World Health Organization, 1997 Jun 3–5
29.
go back to reference Black D, James WPT, Besser GM, et al. Obesity: a report of the Royal College of Physicians. J R Coll Physicians Lond 1983; 17(1): 5–65 Black D, James WPT, Besser GM, et al. Obesity: a report of the Royal College of Physicians. J R Coll Physicians Lond 1983; 17(1): 5–65
30.
go back to reference Garrow JS, Webster J. Quetelet’s index (W/H2) as a measure of fatness. Int J Obes 1985; 9(2): 147–53PubMed Garrow JS, Webster J. Quetelet’s index (W/H2) as a measure of fatness. Int J Obes 1985; 9(2): 147–53PubMed
31.
go back to reference Slaughter MH, Lohman TG, Boileau RA, et al. Skinfold equations for estimation of body fatness in children and youth. Hum Biol 1988; 60(5): 709–23PubMed Slaughter MH, Lohman TG, Boileau RA, et al. Skinfold equations for estimation of body fatness in children and youth. Hum Biol 1988; 60(5): 709–23PubMed
32.
go back to reference Malina RM, Katzmarzyk PT. Validity of the body mass index as an indicator of the risk and presence of overweight in adolescents. Am J Clin Nutr 1999; 70(1): 131–6S Malina RM, Katzmarzyk PT. Validity of the body mass index as an indicator of the risk and presence of overweight in adolescents. Am J Clin Nutr 1999; 70(1): 131–6S
33.
go back to reference Sarria A, Garcia-Llop LA, Moreno LA, et al. Skinfold thickness measurements are better predictors of body fat percentage than body mass index in male Spanish children and adolescents. Eur J Clin Nutr 1998; 52(8): 573–6PubMedCrossRef Sarria A, Garcia-Llop LA, Moreno LA, et al. Skinfold thickness measurements are better predictors of body fat percentage than body mass index in male Spanish children and adolescents. Eur J Clin Nutr 1998; 52(8): 573–6PubMedCrossRef
34.
go back to reference Gray DS, Bray GA, Bauer M, et al. Skinfold thickness measurements in obese subjects. Am J Clin Nutr 1990; 51(4): 571–7PubMed Gray DS, Bray GA, Bauer M, et al. Skinfold thickness measurements in obese subjects. Am J Clin Nutr 1990; 51(4): 571–7PubMed
35.
go back to reference Kyle UG, Genton L, Karsegard L, et al. Single prediction equation for bioelectrical impedance analysis in adults aged 20–94 years. Nutrition 2001; 17(3): 248–53PubMedCrossRef Kyle UG, Genton L, Karsegard L, et al. Single prediction equation for bioelectrical impedance analysis in adults aged 20–94 years. Nutrition 2001; 17(3): 248–53PubMedCrossRef
36.
go back to reference Lukaski HC, Bolonchuk WW, Hall CB, et al. Validation of tetrapolar bioelectrical impedance method to assess human body composition. J Appl Physiol 1986; 60(4): 1327–32PubMed Lukaski HC, Bolonchuk WW, Hall CB, et al. Validation of tetrapolar bioelectrical impedance method to assess human body composition. J Appl Physiol 1986; 60(4): 1327–32PubMed
37.
go back to reference Thomsen TK, Jensen VJ, Henriksen MG. In vivo measurement of human body composition by dual-energy x-ray absorptiometry (DXA). Eur J Surg 1998; 164(2): 133–7PubMedCrossRef Thomsen TK, Jensen VJ, Henriksen MG. In vivo measurement of human body composition by dual-energy x-ray absorptiometry (DXA). Eur J Surg 1998; 164(2): 133–7PubMedCrossRef
38.
go back to reference Vettorazzi C, Smits E, Solomons NW. The interobserver reproducibility of bioelectrical impedance analysis measurements in infants and toddlers. J Pediatr Gastroenterol Nutr 1994; 19(3): 277–82PubMedCrossRef Vettorazzi C, Smits E, Solomons NW. The interobserver reproducibility of bioelectrical impedance analysis measurements in infants and toddlers. J Pediatr Gastroenterol Nutr 1994; 19(3): 277–82PubMedCrossRef
Metadata
Title
Quantification of Lean Bodyweight
Authors
Sarayut Janmahasatian
Dr Stephen B. Duffull
Susan Ash
Leigh C. Ward
Nuala M. Byrne
Bruce Green
Publication date
01-10-2005
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 10/2005
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200544100-00004

Other articles of this Issue 10/2005

Clinical Pharmacokinetics 10/2005 Go to the issue