Population pharmacokinetics and pharmacodynamics of enoxaparin in obese patients
Bruce Green and Stephen Duffull
School of Pharmacy, University of Queensland, Brisbane, Australia
Background Enoxaparin dosing is currently based on total body weight. It is not known how to dose adjust patients who are overweight or obese. This population PKPD study was undertaken to determine a suitable dosing strategy for such patients.
Methods Ninety six patients were recruited in the study. Patients were stratified according to body mass index such that one third of patients had a body mass index <24.9 kg/m2 (normal weight), one third from 25-29.9 kg/m2 (overweight) and one third >30 kg/m2 (obese). Approximately three blood samples were taken per patient to determine anti Xa concentration. The occurrence of bruising was also recorded.
Results Analysis was undertaken using NONMEM (version 5). A two compartment linear model with additive error was fitted to the data. Population estimates for clearance (CL) and central volume compartment (V2) (± SE) were 0.9 (0.07) L.hr-1 and 3.7(0.87) L respectively. Peripheral volume (V3) was estimated at 12.7 (6.1) L, absorption rate constant (Ka) at 0.181 (0.0411) hr-1 and the intercompartmental clearance (Q) at 0.356 (0.175) L.hr-1 with between subject variability of Cl and V2 estimated at 41.7% (39) and 67.6% (29) respectively. Post hoc estimates of CL for each patient were correlated with ideal body weight (r2=0.183), lean body weight (r2=0.212) and sex. V2 was correlated with total body weight (r2=0.22), body surface area (r2=0.203) and body mass index (r2=0.197). The covariate analysis showed CL was best described by lean body weight, and V2 by total body weight. The probability of bruising was modelled using logistic regression and was best described by Cmax and age.
Conclusions Current dosing guidelines for enoxaparin are 100IU/Kg - total body weight every twelve hours. Our findings suggest that this dosing strategy is suitable for patients who weigh less than 120Kg, and those above this weight should be dosed at 100IU/Kg - lean body weight every eight hours.