Veber B, Pocidalo J J
INSERM, U13, Groupe Hospitalier Bichat, Claude-Bernard, Paris, France.
Pathol Biol (Paris). 1995 Jun;43(6):524-8.
The relations between the clinical efficacy, phagocytic transport phenomena, tissular and sera kinetics have been assessed in a pneumonia murine model. At first, the correlation between the clinical efficacy and pharmacokinetics characteristics has been studied for the erythromycin, spiramycin, roxithromycin, clarithromycin and azithromycin. An in vivo clinical efficacy hierarchy has been established (azi > ery > roxi = azi > spira). A hierarchy identical to the clinical efficacy, has been recognised for the pulmonary elimination half lives and the pulmonar AUC. These could be considered as predictive of these antibiotics activity in the respiratory infections. In a second time, the tissular pharmacokinetics of the azithromycin in leukopenic mice allowed to confirm the leukocytes role in the transport and release of this antibiotic in the midst of the infections site. Finally, this antibiotic demonstrated its efficacy in a bacterienic infection even when administered at a low dosage thus allowing to have sera concentrations identical to those obtained in human clinical case and close to MIC's for S. pneumoniae. The pharmacokinetic novelty displayed by its strong tissular penetration can explain its remarkable efficacy.
在肺炎小鼠模型中评估了临床疗效、吞噬转运现象、组织和血清动力学之间的关系。首先，研究了红霉素、螺旋霉素、罗红霉素、克拉霉素和阿奇霉素的临床疗效与药代动力学特征之间的相关性。建立了体内临床疗效等级（阿奇霉素>红霉素>罗红霉素=克拉霉素>螺旋霉素）。对于肺部消除半衰期和肺部AUC，已确认其等级与临床疗效相同。这些可被视为这些抗生素在呼吸道感染中活性的预测指标。其次，阿奇霉素在白细胞减少小鼠中的组织药代动力学证实了白细胞在感染部位该抗生素转运和释放中的作用。最后，这种抗生素即使在低剂量给药时也在细菌性感染中显示出疗效，从而使血清浓度与人临床病例中获得的浓度相同，且接近肺炎链球菌的最低抑菌浓度。其强大的组织穿透力所显示的药代动力学新奇性可以解释其显著的疗效。
