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Encyclopedia of Physical Science and Technology EN011J-559 July 25, 2001 18:57

812 Pharmacokinetics

FIGURE 6 Drug distribution and elimination: detailed considerations. See text.

space and the circulation. Depending on the drug, these dex is the ideal body weight (IBW), which is based on
compartments may need to be included in detailed phar- height:
macokinetic calculations for patients with these disease
states. IBW men = 50 kg + 2.3kg
× (in. of height greater than 5 ft) (13a)
A. Volume of Distribution
IBW women = 45.5kg + 2.3kg
In order to calculate the dose needed to arrive at an ef-
fective drug concentration in the patient’s plasma, the × (in. of height greater than 5 ft). (13b)
magnitude of V d is needed (C = dose/V d ). To eliminate
the need for collection of pharmacokinetic data on each Obesity is a major problem in over 50% of the adult pop-
patient, standard methods of calculating V d with easily ulation of the United States. Since part of the adipose
measured quantities in each patient have been developed. tissue is water, significant amounts of fat can increase
Since few patients weigh an ideal 70 kg, pharmacologists the V d of even the most hydrophilic drug. For patients
have attempted to correlate the loading dose with body who are obese (>20% above ideal body weight), there
weight or body surface area. Recent studies have found is an increase in the effective LBM as well as in adi-
that lean body mass (LBM) is a better predictor of the pose tissue. To take this into account, 20–40% of the
body compartment size V d than is the total body weight. total body weight above the IBW should be added to
LBM is defined as body cell mass, extracellular water, and the IBW to obtain the LBM. Surprisingly, moderately
nonfat intercellular connective tissue (bone, tendons, lig- lipophilicdrugshavenotbeenshowntorequireadjustment
aments, basement membranes). LBM may be calculated in obesity, other than to take into account the additional
as follows: LBM. However, some highly lipophilic drugs, such as
phenytoin, verapamil, lidocaine, and the benzodiazepines,
2
LBM men = 1.10TBM − 120(TBM/height) , (12a) distribute to a significantly larger volume than LBM
in cases of severe obesity, while others (cyclosporine,
2
LBM women = 1.07TBM − 148(TBM/height) , (12b)
propanolol, and prednisolone) do not. The following equa-
where height is in centimeters and LBM and total body tion is based on limited data and should be considered
weight or mass (TBM) is in kilograms. A related in- an approximate solution to the problem of accounting