title: A multi-dose pharmacokinetic study of dalteparin in haemodialysis patients.
abstract: 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 performed a 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 day 2 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.
authors.affiliation: Hemostasis and Thrombosis Center, Duke University Health System, Box 3422, Room 0563, Stead Building, Durham, NC 27710, USA. perry052@mc.duke.edu
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Perry
authors.forename: Susan I
authors.initials: SI
authors.lastname: O'Shea
authors.forename: Stephen
authors.initials: S
authors.lastname: Byrne
authors.forename: Lynda A
authors.initials: LA
authors.lastname: Szczech
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ortel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001835:Body Weight; D017985:Dalteparin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D065427:Factor Xa Inhibitors; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D006435:Renal Dialysis
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D017985:Dalteparin