Lean body mass as a predictor of drug dosage. Implications for drug therapy

Abstract

There is mounting evidence to suggest that lean body mass (LBM) may be a better predictor of drug dosage than either total bodyweight (TBW) or body surface area (BSA), although the rationale for this is not clear. LBM, which is similar but not identical to fat-free mass, can be determined by many different methods. A simple equation based on TBW and height, or determination by bioelectrical impedance are probably the most suitable for use in drug disposition studies. Volume of distribution of relatively hydrophilic drugs correlates very well with LBM, with correlation coefficients of up to 0.9. LBM can be used to accurately predict the loading dose required for these drugs to attain a target peak plasma concentration. For lipophilic drugs, volume of distribution correlates better with TBW than with LBM. Investigation of the relationship between renal drug clearance and LBM has received little attention, probably because creatinine clearance is a useful and readily available marker of renal function. However, limited data suggest that creatinine clearance and LBM together may account function. However, limited data suggest that creatinine clearance and LBM together may account for more variability in renal clearance than creatinine clearance alone. For many drugs eliminated predominantly by the liver, there is a good correlation between systemic clearance and LBM. Such a correlation could be due to a correlation between systemic clearance and liver size or liver blood flow, which has been demonstrated for a few drugs, and a correlation between LBM and liver size and blood flow. The presence of a relationship between LBM and organ size and blood flow has, however, not been investigated to date. A good correlation between drug clearance and LBM indicates that LBM may be an accurate predictor of maintenance dosage, especially in obese patients, in whom there is a large discrepancy between LBM and TBW. BSA is an accurate predictor of drug dosage in infants and children, but whether LBM is superior to BSA in this population remains to be determined. In most studies in adults in which dosage based on LBM has been evaluated prospectively, LBM has been shown to be superior to other measures of body size as a predictor of drug dosage.