Depression of the N-demethylation of erythromycin, azithromycin, clarithromycin and clindamycin in murine Toxoplasma infection

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 the 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%). Copyright (C) 1996 Australian Society for Parasitology. Published by Elsevier Science Ltd.