Berg-Candolfi M, Candolfi E
Institut de Parasitologie, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Int J Parasitol. 1996 Nov;26(11):1321-3. doi: 10.1016/s0020-7519(96)00111-7.
The N-demethylation of macrolides was studied in a murine model of infection. Mice were infected with a cystogenic strain of Toxoplasma gondii (20 or 40 cysts/mouse) and microsomes were prepared from liver homogenates and jejunum villus tip enterocytes on day 10 post-infection. The rate of N-demethylation of the anti-Toxoplasma macrolides azithromycin, clarithromycin and clindamycin was investigated and compared to that of the macrolide erythromycin, a marker of activity of the cytochrome P-450 3A (CYP3A) mono-oxygenases. In infected mice (20 cysts/mouse), the rate of N-demethylation fell in the liver and jejunum for erythromycin (-25% and -35%, respectively), azithromycin (-12% and -10%, respectively), clarithromycin (-23% and -21%, respectively) and clindamycin (-20% and -28%, respectively). The degree of hepatic depression was more marked in mice receiving a 40-cysts burden: for erythromycin (-54%), azithromycin (-29%), clarithromycin (-49%) and clindamycin (-47%).
在小鼠感染模型中研究了大环内酯类药物的N-去甲基化。小鼠感染了产囊的刚地弓形虫株（每只小鼠20或40个包囊），并在感染后第10天从肝脏匀浆和空肠绒毛顶端肠上皮细胞制备微粒体。研究了抗弓形虫大环内酯类药物阿奇霉素、克拉霉素和克林霉素的N-去甲基化速率，并与细胞色素P-450 3A（CYP3A）单加氧酶活性标志物大环内酯类药物红霉素的速率进行比较。在感染小鼠（每只小鼠20个包囊）中，红霉素在肝脏和空肠中的N-去甲基化速率下降（分别为-25%和-35%），阿奇霉素（分别为-12%和-10%），克拉霉素（分别为-23%和-21%）和克林霉素（分别为-20%和-28%）。接受40个包囊负荷的小鼠肝脏抑制程度更明显：红霉素为-54%，阿奇霉素为-29%，克拉霉素为-49%，克林霉素为-47%。
