Abstract
Objective
To develop a standard weight descriptor that can be used for estimation of patient size for obese patients.
Patients and methods
Data were available from 3849 patients: 2839 from oncology patients (index data set) and 1010 from general medical patients (validation data set). The patients had a wide range of age (16–100 years), weight (25–165kg) and body mass index (BMI) [12–52 kg/m2] in both data sets. From the normal-weight patients in the oncology data set, an equation for male and female patients was developed to predict their normal weight as the sum of the lean body mass and normal fat body mass. The equations were evaluated by predicting the weight of patients in the general medical data set who had a normal BMI (<25 kg/m2). In addition, the clinical utility of the predicted normal weight (PNWT) descriptor was assessed by (i) comparing body surface area and allometric scaling calculations based on actual weight of obese patients versus PNWT; and (ii) comparing the predictive performance of creatinine clearance using the Cockcroft and Gault equation when using actual weight of obese patients versus PNWT to predict gentamicin clearance.
Results
The PNWT equations developed from the oncology data set predicted accurately the actual weight of normal weighted (BMI <25 kg/m2) general medical patients (R2 = 0.968 men, R2 = 0.946 women). Using actual weight when computing body surface area and when allometric scaling for obese patients results in significant overestimation of patient size, especially for female patients and those with BMIs >35 kg/m2. The use of PNWT in the Cockcroft and Gault equation provided better predictions of gentamicin clearance than when using actual weight.
Conclusions
A standard weight descriptor has been developed that can be used in dosing algorithms for patients who are obese (BMI >30 kg/m2).
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References
Cheymol G. Clinical pharmacokinetics of drugs in obesity: an update. Clin Pharmacokinet 1993; 25: 103–14
Georges C. Effects of obesity on pharmacokinetics. Implications for drug therapy. Clin Pharmacokinet 2000; 39: 215–31
Dooley MJ, Singh S, Poole SG, et al. Distribution and discordance of body surface area (BSA) and body mass index (BMI) in 4514 patients with malignancy: the utility of BMI to identify obese patients and its implications in BSA adjusted dosing of cytotoxics [abstract]. Proc Am Soc Clin Oncol 2002; 21: 356
Devine B. Case study number 25: gentamicin therapy. Drug Intel Clin Pharm 1974; 8: 650–5
James W. Research on obesity. London: Her Majesty’s Stationary Office, 1976
Cheymol G. Effects of obesity on pharmacokinetics. Clin Pharmacokinet 2000; 39: 215–31
Green B, Duffull SB. Caution when using lean bodyweight as a size descriptor for obese subjects. Clin Pharmacol Ther 2002; 72: 743–4
Anastasio P, Spitali L, Frangiosa A, et al. Glomerular filtration rate in severely overweight normotensive humans. Am J Kidney Dis 2000; 35: 1144–8
Nowack R, Raum E, Blum W, et al. Renal hemodynamics in recent-onset type II diabetes. Am J Kidney Dis 1992; 20: 342–7
DuBois D, DuBois EF. A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med 1916; 17: 863–71
Mosteller RD. Simplified calculation of body surfaced area [letter]. N Engl J Med 1987; 22: 1098
Holford NH. A size standard for pharmacokinetics. Clin Pharmacokinet 1996; 30: 329–32
Felici A, Verweij J, Sparreboom A. Dosing strategies for anti-cancer drugs: the good, the bad and body-surface area. Eur J Cancer 2002; 38: 1677–84
Gurney H. Dose calculation of anticancer drugs: a review of the current practice and introduction of an alternative. J Clin Oncol 1996; 14: 2590–611
Begg EJ, Barclay ML, Duffull SB. A suggested approach to once-daily aminoglycoside dosing. Br J Clin Pharmacol 1995; 39: 335–9
Duffull SB, Kirkpatrick CMJ, Begg EJ. Comparison of two Bayesian approaches to dose-individualisation for once-daily aminoglycoside regimens. Br J Clin Pharmacol 1997; 43: 125–35
Kirkpatrick CMJ, Duffull SB, Begg EJ. Pharmacokinetics of gentamicin in 957 patients with varying renal function dosed once daily. Br J Clin Pharmacol 1999; 47: 637–43
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31–41
Pesola GR, Akhavan I, Madu A, et al. Prediction equation estimates for creatinine clearance in the intensive care unit. Intensive Care Med 1993; 19: 39–43
Gusella M, Toso S, Ferazzi E, et al. Relationships between body composition parameters and fluorouracil pharmacokinetics. Br J Clin Pharmacol 2002; 54: 131–9
Green B, Duffull SB. Development of a dosing strategy for enoxaparin in obese patients. Br J Clin Pharmacol 2003; 56: 96–103
Fisher DM, Reynolds KS, Schmith VD, et al. The influence of renal function on the pharmacokinetics and pharmacodynamics and simulated time course of doxacurium. Anesth Analg 1999; 89: 786–95
Acknowledgements
The authors would like to thank Prof. N. Holford and Prof. G. Graham for lively discussions about patient size, and Prof. G. Toner and Dr M. Michael for their practical input into potential applications.
No sources of funding were used to assist in the preparation of this study. The authors have no conflicts of interest that are directly relevant to the content of this study.
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Duffull, S.B., Dooley, M.J., Green, B. et al. A Standard Weight Descriptor for Dose Adjustment in the Obese Patient. Clin Pharmacokinet 43, 1167–1178 (2004). https://doi.org/10.2165/00003088-200443150-00007
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DOI: https://doi.org/10.2165/00003088-200443150-00007