4
Department of Hematology Cork, University Hospital and the College, Cork, Ireland
5
School of Pharmacy, University College, Cork, Ireland
,
Stephen Byrne
5
School of Pharmacy, University College, Cork, Ireland
,
Lynda A. Szczech
2
Nephrology in the Department of Medicine, Duke University Health System, Durham, North Carolina, USA
,
Thomas L. Ortel
1
Division of Hematology, Duke University Health System, Durham, North Carolina, USA
3
Pathology, Duke University Health System, Durham, North Carolina, USA
› Author AffiliationsFinancial support: This research was conducted in the General Clinical Research Center at Duke University Medical Center (grant# MO1-RR-30, National Center for Research Resources, General Clinical Research Centers Program, National Institutes of Health) and was partially supported by a research grant from Pfizer Global Pharmaceuticals. Additional support included an NIH K-12 award (grant# RR17630–03) for Dr. Perry, a Clinical Scholar Award from the American Society of Hematology and the American Venous Forum Beiersdoff Jobst Research Award for Dr. O’Shea, an NIH K23 (grant# DK02724–01A1) for Dr. Szczech, and a cooperative agreement (U18DD00014) with the Hematologic Diseases Branch, Centers for Disease Control and Prevention, and an NIH award (grant#U54-HL077878) for Dr. Ortel.
Low-molecular-weight heparins undergo renal elimination, and therefore the proper dosing in hemodialysis (HD) patients is unclear. It was the objective of this study to evaluate the pharmacokinetic (PK) parameters of dalteparin in patients receiving chronic HD for end-stage renal disease. We performeda multidose PK study with prophylactic doses of dalteparin in twelve HD patients. Dalteparin 5,000 IU was administered subcutaneously daily for four consecutive days, with HD performed on day2 and day 4. Anti-factor Xa activity was determined daily and at multiple blood samples after the 3rd and 4th dose. Eleven of 12 patients completed the study. The mean (range) PK parameters determined after the 4th dose were as follows: i) maximum concentration (Cmax) was 0.31 IU/ml (0.06 to 0.55 IU/ml); ii) time to Cmax was 3.55 hours (2.59 to 4.96 hr); iii) area under the curve was 3.24 IU*hr/ml (0.64 to 6.44 IU*hr/ml); iv) half-life was 3.82 hr (2.03 to 9.63 hr); and v) trough anti-factor Xa activity 0.04 IU/ml (0.02 to 0.08 IU/ml). No major bleeding was observed. In general, patients with lower body weight exhibited a higher Cmax. From this pilot PK study, we have determined initial PK parameters for dalteparin in HD patients. Although a standard prophylactic dose was used, we found that in this patient population differences in body weight influenced the Cmax. Future studies to evaluate the PK parameters of dalteparin in patients receiving chronic HD may have to use weight-based dosing and will need to be performed over a longer period of time.
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