title: Pharmacodynamics assessment of Bemiparin after multiple prophylactic and single therapeutic doses in adult and elderly healthy volunteers and in subjects with varying degrees of renal impairment.
abstract: BACKGROUND
  Aging and renal impairment may prolong the half-life and lead to accumulation of low molecular weight heparins. Correct dosing is critical to prevent bleeding or thrombosis.
  
  
  METHODS
  Open, parallel study. Healthy adult [n=13] and elderly (>65yrs) [n=12] volunteers; and subjects with mild (ClCr≥50 to ≤80mL/min, n=8), moderate (ClCr≥30 to <50mL/min, n=7), and severe (ClCr<30mL/min, n=8) renal impairment received four prophylactic doses (3,500IU/24h) and a single therapeutic dose (115IU/kg) of bemiparin with an interim washout period. Anti-FXa activity and the potential need for dose adjustment were evaluated.
  
  
  RESULTS
  There were statistically significant differences in the severe renal impairment group vs. adult volunteers in all anti-FXa related parameters, but no significant differences in any of the anti-FXa related parameters between the adult and the elderly. Anti-FXa simulations after 10 prophylactic doses predicted mean Amax=0.59IU/mL in subjects with severe renal impairment and 0.33-0.39IU/mL in the rest. Simulations in the severe renal impairment group with dose adjustment (2,500IU/24h) predicted all individual Amax<0.60IU/mL (mean Amax=0.42IU/ml). Simulations after 10 therapeutic doses predicted mean Amax=1.22IU/mL in severe renal impairment group and 0.89-0.98IU/mL in the rest. Simulations in the severe renal impairment group with 75% dose adjustment predicted individual Amax≤1.60IU/mL (mean Amax=0.91IU/mL).
  
  
  CONCLUSIONS
  No dose adjustments are required in elderly with preserved renal function. A dose adjustment of bemiparin is only advisable in patients with severe renal impairment when using prophylactic or therapeutic doses.
authors.affiliation: Centre d'lnvestigació de Medicaments (CIM-Sant Pau), Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Departament de Farmacologia, Terapeutica i Toxicologia, Universitat Autonoma de Barcelona, Spain. Electronic address: sricoa@hotmail.com.
authors.forename: Salvador
authors.initials: S
authors.lastname: Rico
authors.affiliation: Centre d'lnvestigació de Medicaments (CIM-Sant Pau), Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Departament de Farmacologia, Terapeutica i Toxicologia, Universitat Autonoma de Barcelona, Spain.
authors.forename: Rosa-María
authors.initials: RM
authors.lastname: Antonijoan
authors.affiliation: Centre d'lnvestigació de Medicaments (CIM-Sant Pau), Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Departament de Farmacologia, Terapeutica i Toxicologia, Universitat Autonoma de Barcelona, Spain.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Ballester
authors.affiliation: R&D Department Laboratorios Farmacéuticos Rovi, S.A., Granada, Spain.
authors.forename: Ibon
authors.initials: I
authors.lastname: Gutierro
authors.affiliation: Medical Department, Laboratorios Farmacéuticos Rovi, S.A., Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ayani
authors.affiliation: Medical Department, Laboratorios Farmacéuticos Rovi, S.A., Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Gonzalez
authors.affiliation: Hemostasis and Thrombosis Unit, Department of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Borrell
authors.affiliation: Hemostasis and Thrombosis Unit, Department of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Fontcuberta
authors.affiliation: Centre d'lnvestigació de Medicaments (CIM-Sant Pau), Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Departament de Farmacologia, Terapeutica i Toxicologia, Universitat Autonoma de Barcelona, Spain.
authors.forename: Ignasi
authors.initials: I
authors.lastname: Gich
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000378:metabolism*; D054556:Venous Thromboembolism / Q000517:prevention & control
chemical_list: D006495:Heparin, Low-Molecular-Weight; C411345:bemiparin
keywords: Anti-Factor Xa; Bemiparin; Elderly; Low molecular weight heparins; Pharmacodynamics; Renal impairment