Development of a dosing strategy for enoxaparin in obese patients

Aims Enoxaparin dosing is currently based on total body weight. It is not known how to dose adjust for patients who are overweight or obese. This population pharmacokinetic pharmacodynamic (PKPD) study was undertaken to determine a suitable dosing strategy for such patients. Methods Patients admitted to the Royal Brisbane Hospital and prescribed enoxaparin as part of their normal care were eligible for inclusion into the study. Approximately three blood samples were taken per patient to determine anti-Xa concentrations. The occurrence of bruising was also recorded. A population pharmacokinetic-pharmacodynamic analysis using NONMEM was undertaken. Simulations were performed using MATLAB. Results Ninety-six patients were recruited in a prospective study. One-third of patients had a body mass index <24.9 kg m(-2), one-third from 25 to 29.9 kg m(-2), and one-third >30 kg m(-2). A two-compartment linear model with additive error was fitted to the data. A covariate analysis showed clearance was best described by lean body weight and the central volume compartment by total body weight. The probability of bruising using a logistic regression model was best described by C-max and age. Simulations suggest that patients over 50 years of age whose total body weight is >90 kg, or under 50 years of age whose total body weight is >120 kg are likely to have a smoother concentration-time profile and less bruising if a dose of 100 IU kg(-1) (1 mg kg(-1)) based on lean body weight is administered every 8 h. Conclusions Dose adjustments of enoxaparin in obese patients are likely to reduce the prevalence of bruising, although prospective validation of this is required.