Pharmacological Properties of CY 216 and of Its ACLM and BCLM Components in the Rabbit

Peyrou, V.; Lormeau, J C; Caranobe, C; Gabaig, A.M.; Crepon, B.; Saivin, Sylvie; Houin, Georges; Sié, P.; Boneu, B

doi:10.1055/s-0038-1648851

Cited by 10 publications

(9 citation statements)

References 19 publications

(35 reference statements)

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“…ACLM had chains of MW >5,400 Da (5,500–10,000) and BCLM had chains of MW <5,400 Da (2,100–5,300) [22]. The ACLM fraction was shown to have faster clearance measured by anti-Xa activity than both the parent compound and the BCLM fraction.…”

Section: Introductionmentioning

confidence: 99%

Tinzaparin and other low-molecular-weight heparins: what is the evidence for differential dependence on renal clearance?

Johansen

Balchen

2013

Exp Hematol Oncol

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Since low-molecular-weight heparins (LMWHs) are eliminated preferentially via the kidneys, the potential for accumulation of these agents (and an increased risk of bleeding) is of particular concern in populations with a high prevalence of renal impairment, such as the elderly and patients with cancer. The risk of clinically relevant accumulation of anticoagulant activity as a result of a reduction in renal elimination appears to differ between LMWHs. This review describes the elimination pathways for LMWHs and assesses whether the relative balance between renal and non-renal (cellular) clearance may provide a mechanistic explanation for the differences in accumulation that have been observed between LMWHs in patients with impaired renal function. Clearance studies in animals, cellular binding studies and clinical studies all indicate that the balance between renal and non-renal clearance is dependent on the molecular weight (MW): the higher the MW of the LMWH, the more the balance is shifted towards non-renal clearance. Animal studies have also provided insights into the balance between renal and non-renal clearance by examining the effect of selective blocking of one of the elimination pathways, and it is most likely that cellular clearance is increased to compensate for decreased renal function. Tinzaparin (6,500 Da) has the highest average MW of the marketed LMWHs, and there is both clinical and preclinical evidence for significant non-renal elimination of tinzaparin, making it less likely that tinzaparin accumulates in patients with renal impairment compared with LMWHs with a lower MW distribution. On the basis of our findings, LMWHs that are less dependent on renal clearance may be preferred in patient populations with a high prevalence of renal insufficiency.

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Section: Introductionmentioning

confidence: 99%

Tinzaparin and other low-molecular-weight heparins: what is the evidence for differential dependence on renal clearance?

Johansen

Balchen

2013

Exp Hematol Oncol

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“…18 It has been postulated that the mechanisms of heparin catabolism consist of a balance between a saturable elimination via the reticuloendothelial system and the non-saturable renal tubular excretion. [18][19][20] Various clearance studies in animal models and clinical settings have shown that the higher LMWHs such as tinzaparin (6,500 Da) and dalteparin (5,700 Da) have a faster, dose dependent clearance, suggesting greater involvement of the endothelial clearance pathway with increasing molecular weights and less renal clearance dependency. 21,22 Rabbat and his group reported all patients who experienced bleeding on dalteparin thromboprophylaxis had trough anti-X a levels below the detection threshold.…”

Section: Discussionmentioning

confidence: 99%

Treatment with Dalteparin is Associated with a Lower Risk of Bleeding Compared to Treatment with Unfractionated Heparin in Patients with Renal Insufficiency

et al. 2015

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BACKGROUND: Low molecular weight heparins (LMWHs) have been cautiously used in patients with chronic kidney disease (CKD) due to fear of accumulation. Dalteparin, however, has shown minimal tendency to accumulate in patients with CKD and may be safe to use in this patient population. OBJECTIVE: We compared the incidence of clinically significant bleeding in patients with CKD receiving therapeutic doses of dalteparin to that of patients with CKD receiving therapeutic doses of UFH. DESIGN: This was a retrospective cohort study. SUBJECTS: Inpatients with CKD (GFR<60 ml/min) who were treated with therapeutic dalteparin or UFH were included in the study MAIN MEASURES: Primary outcome was major bleeding within 10 days of anticoagulation, identified by ICD-9 code and confirmed by chart review. Demographic characteristics, laboratory values, comorbidities, prior bleeding history and inpatient medications were extracted for each admission from the electronic medical record. Logistic regression models were created to examine the association between choice of anticoagulant and bleeding rates, after adjustment for demographic and clinical characteristics. KEY RESULTS: Dalteparin-treated patients were significantly less likely to experience a major bleed than patients treated with UFH (1.14 % vs. 3.49 %, p<0.001). The reduced likelihood of bleeding associated with dalteparin treatment remained significant after adjustment for patient characteristics (HR 0.39, 95 % CI: 0.21-0.70, p < 0.0001). A stratified analysis for subgroups with GFR< 30 mL/min and with GFR between 30 and 60 mL/min showed that dalteparin was still associated with lower odds of bleeding compared to treatment with unfractionated heparin, but the difference was nonsignificant for GFR< 30 (HR 0.35,), even after adjustment (OR 0.37, 95 % CI: 0.11-1.22). CONCLUSION: In patients with CKD, treatment with therapeutic dose dalteparin was associated with lower rates of bleeding than treatment with unfractionated heparin. For patients with severe CKD (GFR< 30), dalteparin was shown to be at least as safe as unfractionated heparin.KEY WORDS: dalteparin; renal insufficiency; bleed; heparin.

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“…The ®fth experimental group (group VII) was given nadroparin 5 anti-Xa, U/ kg/day (Fraxiparine Ò , Sano®-Dogu, Istanbul, Turkey). 19,21,22 All pharmacological agents were given in a volume of 0.2 mL. In all groups, pharmacological agents, including normal saline, were given for 7 days postoperatively.…”

Section: Methodsmentioning

confidence: 99%

Effects of some pharmacological agents on the survival of unipedicled venous flaps: an experimental study

et al. 2001

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Clinical and experimental studies have been conducted to improve the survival of venous flaps. As a result of these studies, although various survival mechanisms were raised, none obtained satisfactory information. Venous stasis, and the resultant venous thrombosis, is a factor that decreases the survival of venous flaps. In this study, we evaluated the effects of two antiinflammatory agents, etodolac and etofenamate, on the survival of unipedicled venous flaps. In this study, 35 male New Zealand white rabbits (3,500-4,000 g) (70 ears) were used. Perichondrocutaneous flaps, 3 x 4.5 cm in size, were designed and raised, keeping the central veins intact in the middle of venous flap. Central arteries and nerves were ligated and transected both proximally and distally, to prepare unipedicled venous flaps. A silicone sheet was placed between the cartilage tissue and flap, to prevent blood flow and revascularization beneath. The subjects were divided into seven groups, consisting of five rabbits (10 ears). In the negative control group (group I), the single vascular pedicle of venous flaps, central veins were ligated and flaps sutured into their own place as the composite graft. In the positive control group (group II), after venous flaps were prepared, normal saline, 0.2 mL, was given subcutaneously. In the first of five experimental groups (group III), unfractionated heparin (100 U/day) was given subcutaneously. In the second experimental group (group IV), etodolac (5 mg/kg/day) was given subcutaneously. In the third experimental group (group V), etophenamate (5 mg/kg/day) was given orally through a feeding tube. In the fourth experimental group (group VI), parnaparin (5 anti-Xa U/kg/day) was given subcutaneously. In the fifth experimental group (group VII), nadroparin (5 anti-Xa U/kg/day) was given subcutaneously, about 7 days postoperatively. At the eighth postoperative day, surviving areas of venous flaps were measured, and the results were evaluated by Kruskal-Wallis ANOVA and Mann-Whitney U-test (P < 0.05). Biopsies were also taken from the flaps for histological evaluation of border of necrotic tissue. Surviving areas of unipedicled venous flaps were larger in experimental groups than those in negative and positive control group (P < 0.05). However, comparison of the experimental groups demonstrated no statistically significant difference (P > 0.05). We concluded that all pharmacological agents used in the experimental groups succeeded in increasing the survival of unipedicled venous flaps. Survival of the unipedicled venous flap was higher in venous flaps than that of composite graft, clearly showing the importance of the venous pedicle.

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Pharmacological Properties of CY 216 and of Its ACLM and BCLM Components in the Rabbit

Cited by 10 publications

References 19 publications

Tinzaparin and other low-molecular-weight heparins: what is the evidence for differential dependence on renal clearance?

Tinzaparin and other low-molecular-weight heparins: what is the evidence for differential dependence on renal clearance?

Treatment with Dalteparin is Associated with a Lower Risk of Bleeding Compared to Treatment with Unfractionated Heparin in Patients with Renal Insufficiency

Effects of some pharmacological agents on the survival of unipedicled venous flaps: an experimental study

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