The effect of body weight on dalteparin pharmacokinetics. A preliminary study.
OBJECTIVE
To investigate whether there were significant differences in the volume of distribution (V) and clearance (CL) of dalteparin in obese versus normal-weight patients, and thereby determine whether dosing of dalteparin should be based on total body weight, lean body weight or an adjusted body weight in obese patients.


METHODS
Patients (ten obese and ten normal weight) treated with dalteparin were matched for age, gender, lean body weight and creatinine CL. Two steady-state plasma dalteparin concentrations were taken from each patient and assayed in duplicate. The pharmacokinetic values of V and CL were estimated, for each patient, using the Bayesian maximum a posteriori method with the program ABBOTTBASE.


RESULTS
The mean V in obese patients was approximately 60% larger than in normal-weight patients, but this was not statistically significant (P = 0.11; two-tailed). The mean value of V (8.41) in the normal-weight patients was similar to that reported in the literature. The mean difference in values of CL (18% larger in obese patients) was not clinically or statistically significant. A poor correlation was seen between V and lean body weight (r2 = 0.05). There was a moderate correlation between V and total body weight (r2 = 0.52) and between V and adjusted body weight (r2 = 0.55); adjusted body weight = [lean body weight + 0.4(total body weight - lean body weight)]. Total body weight and adjusted body weight provided a better correlation with CL (r2 = 0.39, 0.32, respectively) than did lean body weight (r2 = 0.01).


CONCLUSIONS
These results suggest that doses of dalteparin in obese patients should be based on total body weight or an adjusted body weight, but not lean body weight. This study highlights some potential differences in the pharmacokinetics of dalteparin in individuals who are obese, and further work is necessary to quantify these differences in more detail.
Yee
J Y
JY
Pharmacy Department, Christchurch Hospital, New Zealand. juliey@chhlth.govt.nz
Duffull
S B
SB
D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001499:Bayes Theorem; D001682:Biological Availability; D001835:Body Weight; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D017985:Dalteparin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000493:pharmacokinetics; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D012044:Regression Analysis
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D003404:Creatinine; D017985:Dalteparin