Biochemical and pharmacologic inequivalence of low molecular weight heparins.
LMW heparin fractions obtained from various sources must not be considered as bioequivalent in both the in vitro and in vivo responses. Because of compositional variations, these agents exhibit individual behavior and should be considered as distinct drugs whose safety and efficacy profile must be determined separately. Currently, there is no valid LMW heparin standard available, however, different LMW heparins can be profiled in identical test systems. It is erroneous to assume that most LMW heparins will behave in a similar fashion in terms of safety and efficacy. The need for defined tests to characterized these agents is evident and efforts to profile their actions should be made at both the basic and applied levels. Needless to say, the true efficacy of LMW heparins can only be validated in well-designed randomized clinical trials. Optimization of LMW heparins in preclinical pharmacologic studies, as reported here, is a crucial factor in the development of these agents. The superior clinical efficacy/safety performance of some of the LMW heparins in contrast to other LMW heparins is a result of extensive preclinical pharmacologic investigations undertaken to optimize the therapeutic index of these agents. Such optimization studies have not been conducted during the development of many LMW heparins, resulting in decreased efficacy and undue complications.
Fareed
J
J
Loyola University Medical Center, Maywood, Illinois 60153.
Walenga
J M
JM
Hoppensteadt
D
D
Huan
X
X
Nonn
R
R
D000818:Animals; D001682:Biological Availability; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015951:Factor Xa; D006495:Heparin, Low-Molecular-Weight / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D011323:Primates; D011479:Protamines / Q000494:pharmacology; D011817:Rabbits; D015842:Serine Proteinase Inhibitors; D013927:Thrombosis / Q000188:drug therapy
D006495:Heparin, Low-Molecular-Weight; D011479:Protamines; D015842:Serine Proteinase Inhibitors; D015951:Factor Xa