Are the pharmacokinetic parameters of low molecular weight heparins predictive of their clinical efficacy?

1996 ◽  
Vol 81 (2) ◽  
pp. S29-S38 ◽  
Author(s):  
Konrad Andrassy ◽  
Volker Eschenfelder
Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2308-2308
Author(s):  
Debra Hoppensteadt ◽  
Walter Jeske ◽  
Jeanine M. Walenga ◽  
Bruce E Lewis ◽  
Jawed Fareed

Abstract Abstract 2308 Low molecular weight heparins such as enoxaparin and dalteparin are widely used for the management of Acute Coronary Syndrome (ACS). Recently, several generic versions of enoxaparin and dalteparin have been approved in various countries for all of the branded product's indications. However, no data on their clinical equivalence in ACS is available. Since generic versions of enoxaparin and dalteparin are manufactured by different processes and may use starting material from different sources, these drugs may differ in their pharmacological profile in simulated ACS settings. To compare the pharmacodynamic effects, a branded version of enoxaparin was compared with three generic versions in a primate model at a dosage of 1 mg/kg IV. Such pharmacokinetic parameters as TFPI release, TAFI modulation, vWF release, and TF mediated platelet activation were measured. Anticoagulant effects of these drugs were also measured after IV administration using iSTAT ACT and aPTT. Simulated catheter related thrombosis studies were carried out to differentiate each agent in contact, intrinsic and extrinsic clotting systems. The generic versions of enoxaparin namely, Cutenox (Gland Pharma), Fibrinox (Sandoz AG) and Versa (EuroPharma) exhibited product based pharmacodynamic differences compared with the branded product and the results are provided in the following table. Each of the generic products exhibited its own specific pharmacologic profile despite comparable molecular weight distributions and anti-Xa potencies. Significant differences were noted in the anticoagulant effects of each of these agents as compared with the branded products. Some differences were also noted in HIT antibody mediated aggregation studies. The differences between the branded and generic versions of LMWHs may be due to the higher dosages used and the IV administration which leads to higher circulating levels of these agents. These observations suggest the need for additional animal studies and clinical trials to validate the use of generic versions of LMWHs in such critical indications as ACS and related syndromes. Disclosures: No relevant conflicts of interest to declare.


1998 ◽  
Vol 32 (5) ◽  
pp. 588-601 ◽  
Author(s):  
Pierre Martineau ◽  
Nadine Tawil

OBJECTIVE: To compare the characteristics and clinical efficacy of low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH) in the treatment of deep-vein thrombosis (DVT). Adverse effects, dosing, and cost issues are also discussed. DATA SOURCES: A MEDLINE search (January 1984–October 1997) was used to identify pertinent French and English literature, including clinical trials and reviews on LMWHs and their use in DVT. STUDY SELECTION: Trials comparing dalteparin, enoxaparin, tinzaparin, and nadroparin with UFH were selected. As studies were numerous, only randomized trials including more than 50 patients were reviewed. Moreover, all patients studied had a first episode of symptomatic DVT confirmed by objective tests (i.e., venography, duplex ultrasonography, impedance plethysmography). Clinical efficacy and safety of LMWHs were assessed in these trials. DATA EXTRACTION: Results pertaining to venographic assessment, recurrent thromboembolism, total mortality, and bleeding complications were extracted from the selected studies. DATA SYNTHESIS: Compared with UFH, LMWHs have a longer plasma half-life, better subcutaneous bioavailability, more predictable anticoagulant response, and require less intense laboratory monitoring. Most trials demonstrate comparable effects on thrombus extension and incidence of recurrent thromboembolism. Compared with UFH, LMWHs do not alter total mortality. Although animal trials predict a lower hemorrhagic potential for LMWHs, the incidence of bleeding complications is generally similar to that observed with UFH. Outpatient management of DVT with LMWHs has shown comparable safety and efficacy with inpatient UFH use but a shorter hospital stay. CONCLUSIONS: Because LMWHs are as safe and as effective as UFH, and because of their more convenient method of administration, they can be considered valuable alternatives for the treatment of DVT. Savings generated by less intensive laboratory monitoring and the possibility of early hospital discharge and outpatient therapy may outweigh the higher acquisition cost of LMWHs.


Author(s):  
Е.В. Ройтман ◽  
В.М. Печенников

Низкомолекулярные гепарины (НМГ) являются уникальными препаратами: образуя одну группу, объединенную антитромботическим действием, каждое МНН (международное непатентованное наименование) дополнительно предоставляет свой спектр плейотропного (неантитромботического) действия со своим профилем клинической эффективности. Из-за различий в структуре этих препаратов не следует переносить результаты, полученные с одним НМГ, на другой. Однако различия между ними не делают какой-то один НМГ лучше или хуже другого. Напротив, они позволяют выбрать если не оптимальный, то наиболее подходящий препарат для конкретного пациента. При выборе НМГ для конкретного пациента необходимо строго руководствоваться инструкцией по медицинскому применению и тщательным подбором индивидуальной дозы препарата, исходя из массы тела пациента, степени тяжести заболевания, сопутствующей патологии, а также принимая во внимание ряд других факторов. Low molecular weight heparins (LMWHs) make one pharmacological group due to their antithrombotic action, but each of their international nonproprietary names provides additionally its own spectrum of pleiotropic (non-antithrombotic) actions with a specific profile for clinical efficacy. Due to the differences in the structure of these medications the results obtained with one LMWH should not be transferred to another. However, differences between LMWHs do not make one better or worse than the other. On the contrary, it allows you to choose if not optimal then the most suitable LMWH for the patient taking into account a number of influencing factors as well.


1993 ◽  
Vol 13 (S 01) ◽  
pp. S5-S11 ◽  
Author(s):  
Debra Hoppensteadt ◽  
Jeanine Walenga ◽  
A Ahsan ◽  
O Iqbal ◽  
W Jeske ◽  
...  

SummaryThe introduction of low molecular weight heparins has added a new dimension to the pharmacological management of thrombotic disorders. Because of different chemical and pharmacological characteristics, due to the manufacturing process, each LMWH should be considered as a distinct entitity and only be used for its given indication. A list of commercially available LMWHs is included. The mechanism of action of the LMWHs and their use in various disorders are discussed. Available laboratory tests for monitoring LMWHs are presented and their limitations pointed out.


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