Absorption Distribution Metabolism and Excretion

The macrolides are absorbed from the intestinal tract, although the presence of food interferes with absorption and part of the dose is destroyed because of the relative acid lability of these antimicrobials. To minimize destruction and enhance absorption, erythromycin is administered as a stearate or oleate salt or is enteric coated. Because stearate and estolate erythromycins are not acid labile, the administration of these formulations results in higher blood levels. The O-methyl substitution of erythromycin that results in clarithromycin also confers acid stability and better absorption with food.

The macrolides diffuse readily into tissues and cross placental membranes. CSF levels are about 20% of plasma levels, while biliary concentrations are about 10 times plasma levels. Although the serum levels of clar-ithromycin and azithromycin are low, these antibiotics concentrate in tissue and reach high levels.

Erythromycin and azithromycin are excreted primarily in active form in bile, with only low levels found in urine. Clarithromycin is metabolized to the biologically active 14-OH metabolite and is eliminated largely by the kidney. The half-life of erythromycin is approximately 1.4 hours, whereas the half-life of clarithromycin is 3 to 7 hours and that of azithromycin approaches 68 hours.

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