In man,
clarithromycin (A-56268) is metabolized to a 14-hydroxy derivative (14-
OH clarithromycin,
A-62671); this metabolite is absent in mice. An experimental mouse model was used to compare the efficacy of
clarithromycin versus 14-OH
clarithromycin in
pneumococcal pneumonia by treatment with either the parent
drug or its 14-OH metabolite alone. Four groups of 15 mice were infected intra-tracheally with a virulent strain of Streptococcus pneumoniae serotype 3 (approximately 10(5) cfu/mouse). Treatment was begun 18 h post
infection, with
clarithromycin or
erythromycin 50 mg/kg subcutaneously (sc) bd, 14-OH
clarithromycin 25 mg/kg sc bd or
antibiotic free saline sc bd for 24 or 48 h. Survival rates ten days after one day of treatment with
clarithromycin, 14-OH
clarithromycin,
erythromycin, or saline were 53%, 60%, 27% and 0% respectively. After two days treatment the rates were 100%, 100%, 53% (P less than 0.01) and 0% respectively. Thirty-six h after two doses, 14-OH
clarithromycin demonstrated superior intra-pulmonary killing activity to
erythromycin (2.7 +/- 0.4 vs 6.6 +/- 0.8 log10 cfu/mL lung homogenate) (P less than 0.001) and comparable activity to
clarithromycin (3.6 +/- 1.3 log10 cfu/mL). These results show that
clarithromycin (50 mg/kg sc) and 14-OH
clarithromycin (25 mg/kg sc) have similar in vivo efficacy in a mouse model, in which the 14-OH metabolite is not produced from
clarithromycin. This suggests that in man, the clinical efficacy of
clarithromycin is not impaired by metabolism to 14-OH
clarithromycin, which achieves serum concentrations in man of approximately 1 mg/L after multiple doses of
clarithromycin 500 mg po.