Question 20 from the first paper of 2009 asks the candidates to define ideal body weight, as a segue into a discussion of pharmacokinetic changes in morbid obesity. Apart from the ideal body weight, other measures of body composition play a role in pharmacokinetics. These include the total body weight, the body surface area index, the lean body weight, and the predicted normal weight. Drug dosing in the instructions of the manufacturer may favour one measure over the others, and specific pharmacokinetic properties of various drugs may influence which weight measure you choose to calculate their weight-adjusted dose.

Information regarding this specific topic is quite hard to find. The de Baerdmaeker article from 2004 is probably the most illuminating in terms of discussing ideal body weight and lean body weight. Ingrande and Lemmens (2010) discuss the other measures in brief. These articles were used a sources for the summary offered below.

### Gold standard measure of body composition

- Unfortunately, the gold standard is the
*cadaveric measurement.* - You puree the entire organism and separate the components.
- This is inconvenient in the critical care environment.

### Total body weight and pharmacokinetics

- Dosing recommendations are generally based on TBW
- This is fine for normal people, in whom total body weight is similar to ideal body weight.
- With increasing obesity, fat mass accounts for an increasing amount of total body weight. However, the majority of the cardiac output is still directed to the lean tissue groups.
- Therefore, dosing a drug to total body weight in a morbidly obese individual may result in overdose (imagine, 7mg/kg of gentamicin in a 250kg person would produce an ear-ringing 1750mg dose).

### Ideal body weight and pharmacokinetics

- Who says its "ideal"? Well. The definition is
*"the ideal weight associated with maximum life-expectancy for a given height".* - There are numerous equations, all of which tend to agree (or, close enough for government work). One such equation is:

Ideal body weight (kg) = height (cm) - 100

(100 for males, and 105 or 110 for females.)

Ideally, this technique should tell you what weight a person*should*be, and therefore help you estimate their lean body mass so as to dose their drugs appropriately. - The bizarre assumption made in this calculation is that inside every morbidly obese person there is a mass of lean tissue which is ideal for their maximal life expectancy, and which is directly proportional to their height. All patients of the same height would end up receiving the same dose if you use this metric, no matter how much they weigh.
- This is clearly incorrect, as obese individuals tend to have
*more*lean body mass than normal people (as more muscle is required to carry all the extra weight). - However, in most cases in morbid obesity the volume of distribution of non-lipophilic drugs is fairly stable, and related to IBW.

### Body surface area and pharmacokinetics

- This metric is (purely by tradition) used for dosing of chemotherapy agents, and is virtually identical to the IBW in terms of its disadvantages. Equations used to calculate BSA contain total body weight and height. Mosteller's equation is the most commonly used:
- One such equation is:

BSA (m^{2}) = square root of (height ×weight / 3600)

(height and weight are in cm and kg, respectively) - We have been dosing chemotherapy drugs in this way since the 1950s. (Gurney, 1996). This method was adopted without anybody questioning its validity.
- Like IBW, this method ends up offering a similar dose to patients of the same height.
- Even oncologists admit that "this method does not account for the marked interpatient variation in drug handling" (Gurney, 2002)

### Lean body weight and pharmacokinetics

- Lean body weight is the difference between total body weight and fat mass.
- Lean body weight is significantly correlated to cardiac output.
- It is probably the best method of dose adjustment for morbidly obese patients.
- One equation to estimate LBW is as follows:

Male LBM = 1.1(weight)−128(weight/height)^{2}

Female LBM = 1.07(weight)−148(weight/height)^{2}

(height and weight are in cm and kg, respectively) - Unfortunately, at extremes of morbid obesity this equation underestimates lean body weight and can even yield negative values.

### In summary:

- In people of normal weight, TWB = IBW = LBW and no equations are required.
- Most drug dose instructions refer to TBW.
- In morbidly obese people,
- TBW overestimates the dose.
- IBW underestimates the dose.
- LBW is probably the best estimate of dose.
- In the case of most nonlipophilic drugs, IBW is sufficient because V
_{d}does not change. - In the case of strongly hydrophilic drugs, instead of calculating LBW, 20% can be added to the IBW to account for the increase in lean body tissue content.
- In the case of strongly lipophilic drugs, and in the case of many anaesthetic agents, LBW is the ideal metric.

### References

De Baerdemaeker, Luc EC, Eric P. Mortier, and Michel MRF Struys. "Pharmacokinetics in obese patients." *Continuing Education in Anaesthesia, Critical Care & Pain* 4.5 (2004): 152-155.

Cheymol, Georges. "Effects of obesity on pharmacokinetics." *Clinical pharmacokinetics* 39.3 (2000): 215-231.

Wells, J. C. K., and M. S. Fewtrell. "Measuring body composition." *Archives of Disease in Childhood* 91.7 (2006): 612-617.

Ingrande, J., and H. J. M. Lemmens. "Dose adjustment of anaesthetics in the morbidly obese." *British journal of anaesthesia* 105.suppl 1 (2010): i16-i23.

Mosteller, R. D. "Simplified calculation of body-surface area." *The New England journal of medicine* 317.17 (1987): 1098.

Gurney, H. "How to calculate the dose of chemotherapy." *British journal of cancer* 86.8 (2002): 1297-1302.

Gurney, Howard. "Dose calculation of anticancer drugs: a review of the current practice and introduction of an alternative." *Journal of Clinical Oncology* 14.9 (1996): 2590-2611.