Fareed J, Walenga J M, Hoppensteadt D, Huan X, Nonn R
Loyola University Medical Center, Maywood, Illinois 60153.
Ann N Y Acad Sci. 1989;556:333-53. doi: 10.1111/j.1749-6632.1989.tb22515.x.
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.
从不同来源获得的低分子量肝素组分在体外和体内反应中不能被视为生物等效。由于成分差异，这些药物表现出个体行为，应被视为不同的药物，其安全性和有效性必须分别确定。目前，尚无有效的低分子量肝素标准品，然而，不同的低分子量肝素可以在相同的测试系统中进行分析。假设大多数低分子量肝素在安全性和有效性方面会表现出相似的行为是错误的。显然需要有明确的测试来表征这些药物，并且应该在基础和应用层面努力分析它们的作用。不用说，低分子量肝素的真正疗效只能在精心设计的随机临床试验中得到验证。如本文所述，在临床前药理研究中优化低分子量肝素是这些药物开发的关键因素。与其他低分子量肝素相比，一些低分子量肝素具有卓越的临床疗效/安全性表现，这是为优化这些药物的治疗指数而进行广泛临床前药理研究的结果。许多低分子量肝素在开发过程中并未进行此类优化研究，导致疗效降低和出现不必要的并发症。
