Which weight for weight-based dosage regimens in obese patients?

In addition to age and measures of organ dysfunction, body weight is a variable that is often required to determine the most appropriate medication dosage. Dosage that is inappropriate for the patient’s weight may increase the risk of adverse events and increase the cost of care. In one tertiary care institution, dosage that was inappropriate for patients’ weight and renal function resulted in 42% of all the adverse drug events reported in the investigation. All of these events were considered to be preventable. Each adverse drug event in the study was estimated to result in an excess hospitalization cost of $2262 (p < 0.001 compared to matched controls without events). To avoid the deleterious consequences for both the patient and the institution if inappropriate dosage regimens are used, a number of medications have weight-based (e.g., milligram per kilogram) dosage recommendations. This raises the question, particularly for obese patients, of which weight should be used. Depending on factors such as the relative lipophilicity of the medication, the clinician may choose to use actual or total body weight (TBW) or an adjusted weight, such as ideal body weight (IBW) or some other adjusted weight. In patients who are not obese or extremely underweight, the decision to use TBW or an adjusted weight for calculating medication Copyright © 2002, American Society of Health-System Pharmacists, Inc. All rights reserved. 1079-2082/02/1101-2105$06.00. dosages is of little clinical importance, since either calculation would yield similar results. However, with increasing degrees of obesity, the dosages derived by TBW, IBW, or adjusted weight will be increasingly disparate. The pervasiveness of terms, such as IBW, throughout the pharmacy literature belies the uncertainties surrounding such estimations. The calculations themselves are quite straightforward and are typically learned in pharmacy school. As a clerkship preceptor, I find that most students have memorized an equation for IBW, and those who do not can generally find it in their pharmacokinetics books. But it is much less common that these same students understand the limitations of the equation, the most important of which may be that weight-adjusted calculations may never have been demonstrated to improve patient outcomes, either through increased medication efficacy or reduced toxicity. The purpose of this discussion is to examine the rationale for using a weight other than TBW for weightbased medication calculations in adult obese patients and to elucidate the major limitations of these calculations. Some of the terminology related to weight adjustment that is commonly associated with weightbased dosage regimens will be reviewed, and a discussion of the rationale for common dosing equations will be provided. Obesity-related changes in organ function, which may necessitate alterations in dosage regimens, will be briefly discussed along with the limitations of available pharmacokinetic and pharmacodynamic literature relative to drug dosing in obese patients. Finally, issues related to choosing a weight for the initiation of weight-based dosage regimens will be discussed.