A comparative pharmacodynamic study of anti-Xa activity to evaluate the accumulation effect of Tinzaparin and Enoxaparin given at prophylactic dose over 8 days in elderly patients with impaired renal function

Abstract number: P1871

Aghasaryan^* M., Mazoyer† E., Mah醠I., dit Bal Sollier† C., Simoneau^* G., Berge† N., Soulat‡ T., Bergmann† J. - F., Heilmann§ J.-J., Drouet† L., Caulin† C.

‡Hematology Laboratory, Lariboisière Hospital, France; ^*Internal Medicine Department A, Lariboisière Hospi, France; †Lariboisière Hospital, France; §Leo-Pharma, France

Rationale  

LMWHs accumulate in patients with impaired renal function. As this accumulation depends on heparin chain length and subsequent reticuloendothelial/renal elimination/catabolism LMWHs of different degree of depolymerization (different distribution and length of heparin chains) should have different pharmacodynamic profile. Do these differences contribute to accumulation of LMWHs in case of renal insufficiency?

Patients, methods and material  

An open randomized parallel trial is conducted with a primary objective to detect any accumulation effect of two LMWHs, Enoxaparin and Tinzaparin, at repeated administration of the prophylactic dose over 8 days in elderly patients with impaired renal function (creatinine clearance between 20 and 50 mL min^-1) and low body weight (<65 kg). 60 hospitalized medical patients will be included in the trial. After enrollment of 30 patients the study population has a mean age of 90 ± 4.9 years, a mean renal creatinine clearance of 34.6 ± 14.4 mL min^-1 and a mean body weight of 51.4 ± 7.5 kg. Patients are randomized in two parallel groups and receive either Enoxaparin (Lovenox®) 4000 IU, or Tinzaparin (Innohep®) 4500 UI. The anti-Xa and the anti-IIa activities are hourly measured on the 1st and the 8th days of treatment. Blood samples are taken at 0, 2, 4, 5, 6, 9, 12, 16, 24 h after the injection of the study drug. The primary end point is the accumulation factor calculated as a ratio between the maximal Anti-Xa activity (Amax) observed on day 8 and the Amax observed on day 1. We also compare the values of AUC 0–24 (area under the time activity curve 0–24 h post dosing) and Amin (residual activity 24 h after the injection) observed on day 8 with the respective values observed on day 1. The analysis of pharmacodynamic data is blinded with regard to the allocation of treatment.

Results  

The last patients are currently being recruited. The biological analyses are scheduled for the first trimester 2003 and results will be presented.