Designing drug regimens for special intensive care unit populations

Table 6 Assessment of possible dose proportionality in studies with obese subjects¹

Did the study involve a comparator group of normal weight subjects of similar demographics (e.g., age, height, gender) and co-morbidities as the obese subjects?

Did the values of pharmacokinetic parameters unadjusted for bodyweight (e.g., volume of distribution in mL and clearance in mL/min) increase proportionally to weight in the obese vs the normal-weight subjects?

Were the values of pharmacokinetic parameters adjusted for actual bodyweight (e.g., volume of distribution in mL/kg and clearance in mL/min per kilogram) similar in the obese and normal-weight subjects?

Did the values of pharmacokinetic parameters adjusted for ideal bodyweight (e.g., volume of distribution in mL/kg and clearance in mL/min per kilogram) increase proportionally to weight in the obese vs the normal-weight subjects?

Was the calculated half-life based on the pharmacokinetic parameters similar in the obese and normal-weight subjects?

When actual bodyweight was used in weight-based dosing protocols were the therapeutic effects and dose-related adverse drug events similar in the obese and normal-weight subjects?

¹If the answers to all of these questions are yes, the data suggests that dose proportionality is present, although this does not necessarily mean that actual bodyweight should be used in weight-based dosing protocols. Reprinted with permission from Erstad[15]. Copyright © by John Wiley Sons, Inc. Reprinted by permission of John Wiley & Sons, Inc.