Kinetics and mechanisms of action of drugs on microorganisms. XV. Effect of erythromycin on the action of lincomycin (Phase II) and the 7 (S)-chloro analogs of lincomycin against Escherichia coli.
Kinetics and mechanisms of action of drugs on microorganisms. XV. Effect of erythromycin on the action of lincomycin (Phase II) and the 7 (S)-chloro analogs of lincomycin against Escherichia coli.
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药物对微生物的动力学和作用机制。
DOI：
10.1002/jps.2600610410
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发表时间：
1972
影响因子：
3.8
通讯作者：
E. R. Garrett
中科院分区：
文献类型：
--
作者：
S. M. Heman;E. R. Garrett
林可霉素影响的大肠杆菌培养物显示两个阶段的稳态生成。初始（I期）稳态生成，表示为In N = kapp.It +常数，在相同剂量水平下，几代之后是最终（II期）稳态生成，In N = kapp.IIt +常数，其中kapp.I > kapp. II。受红霉素或林可霉素的7（S）-氯类似物影响的培养物仅显示一个稳态代。乳糖酸红霉素-盐酸林可霉素（I相）的固定效价比为1：5（以重量计），在宽的药物浓度范围内有效。红霉素和林可霉素的组合可根据该效力因子定量，其作用与等效林可霉素（在I相作用中）或红霉素单独作用具有动力学等效性。然而，红霉素和林可霉素（II期）的效价因子随浓度水平而变化。因此，红霉素和林可霉素的组合，其先验地具有与单独的等效林可霉素相同的效力（在I相作用中），在II相作用中效力较低。这归因于混合物II相作用中稀释林可霉素效应的人为因素，而不是效应的拮抗作用。红霉素和林可霉素的7（S）-氯类似物的组合证明了作用的先验拮抗作用，因为可能的变构相互作用降低了一种药物在其作用位点存在另一种药物时的作用。强调在抗生素联合作用的定量和预测中，必须考虑在较宽浓度范围内的剂量-反应关系，以及单独药物作用的动力学和机制。
Lincomycin-affected Escherichia coli cultures show two phases of steady-state generation. The initial (Phase I) steady-state generation, expressed as In N = kapp.It + constant, is followed after several generations by an ultimate (Phase II) steady-state generation, In N = kapp.IIt + constant, at the same dose level, where kapp.I > kapp.II. Cultures affected with erythromycin or the 7(S)-chloro analogs of lincomycin show only one steady-state generation. A fixed potency ratio of erythromycin lactobionate-lincomycin hydro-chloride (Phase I) as 1:5 (on weight basis) is operative over a wide drug concentration range. Combinations of erythromycin and lincomycin are quantifiable on the basis of this potency factor as kineti-cally equivalent in action to the equipotent lincomycin (in Phase I action) or erythromycin alone. However, the potency factor for erythromycin and lincomycin (Phase II) varies with the concentration level. Therefore, combinations of erythromycin and lincomycin, which a priori have the same potency as equivalent lincomycin alone (in Phase I action), are less potent in the Phase II action. This is attributed to an artifact of diluted lincomycin effect in Phase II action of the mixture and not to antagonism of effects. Combinations of erythromycin and the 7(S)-chloro analogs of lincomycin demonstrate a priori antagonism of effects because of possible allosteric interactions which decrease the effects of one drug in the presence of the other at their site of action. It is emphasized that the dose-response relationship over a wide concentration range, as well as the kinetics and mechanisms of the separate drug action, must be considered in the quantification and prediction of combined action of antibiotics.