Ecological impact of doxycycline at low dose on normal oropharyngeal and intestinal microflora

This study included 34 healthy volunteers (16 male and 18 female) aged 19-37 years, of whom 17 received doxycycline 40 mg capsules orally once daily (o.d.) and 17 received placebo 40 mg capsules orally o.d. for 16 weeks. Plasma, saliva and faecal samples were collected before drug administration and at 4, 8, 16 and 20 weeks. Plasma samples were assayed for doxycycline concentrations, and saliva and faecal samples were investigated for doxycycline concentrations and microbiological analyses. Plasma concentrations of doxycycline in the doxycycline group were as follows: baseline visit (2 h), 0.20-0.61 mg/L; 4-week visit, 0.30-1.04 mg/L; 8-week visit, 0.43-1.49 mg/L; 16-week visit, 0.32-1.12 mg/L; and 20-week visit 0 mg/L. No doxycycline was detected in plasma in the placebo group. No doxycycline concentrations in the saliva samples were found in the doxycycline or placebo groups at the five visits. Faecal concentrations of doxycycline in the doxycycline group were as follows: baseline visit, 0 mg/kg; 4-week visit, 0-3.71 mg/kg; 8-week visit, 0-1.85 mg/kg; 16-week visit, 0-4.10 mg/kg; and 20-week visit, 0 mg/kg. No doxycycline faecal concentrations were detected in the placebo group. Minor effects on the aerobic and anaerobic oropharyngeal microflora were observed both in the doxycycline and placebo groups. There were minor changes in the number of enterococci and Escherichia coli in the doxycycline and placebo groups. The anaerobic intestinal microflora in the doxycycline and placebo groups was not changed, and no Clostridium difficile strains were isolated.