Efficacy of ganciclovir in combination with other antimicrobial agents against cytomegalovirus in vitro and in vivo

Abstract In MRC-5 cell cultures, the efficacy of the acyclic nucleoside ganciclovir (GCV) against human cytomegalovirus (CMV) was unaffected when combined with either amphotericin B (AMP B), ketoconazole (KCZ), dapsone (DAP), or trimethoprim/sulfamethoxazole (TMP/SMX). When differences in 3-dimensional plots for antiviral activity and cytotoxicity of GCV alone and in combination were compared, the anti-CMV activity of GCV (IC 50 8 μM, 5–9 μM range) was not affected by concentrations of up to 10 μM AMP B, 1000 μM KCZ, 100 μM DAP or 320 μM TMP/SMX (higher concentrations could not be tested due to cytotoxicity). In Swiss Webster mice, the anti-CMV activity of GCV was also unaffected when administered in combination with any of the four other antimicrobial agents against murine CMV. GCV (s.c.) alone had an ED 50 of 7 mg/kg (2–12 mg/kg range) which was unaffected by daily doses of 1 mg/kg AMP B (i.p.), 60 mg/kg KCZ (i.p.), 32 mg/kg DAP (p.o.) or 80/400 mg/kg TMP/SMX (p.o.). These results suggest that GCV can be administered in combination with these other drugs for treatment of various opportunistic infections in AIDS patients without compromising the efficacy of GCV against CMV.