Fusidic acid pharmacology, pharmacokinetics and pharmacodynamics

Fusidic acid comes in a variety of formulations for oral, intravenous and topical use. After oral administration of 500 mg Cmax values range from 14.5-3.3 mg/l and an elimination half-life of 8.9-11.0 h. Similar values are obtained with intravenous administration of the sodium salt, although peaks tend to be higher. Bioavailability for the new film-coated tablet is approximately 91% while that of the suspension formulation appears to be much lower. Repeated dosing results in substantial drug accumulation when given 8-hourly, and to a variable extent depending on dose when administered 12-hourly. One study has demonstrated a modest dose-dependency for pharmacokinetics, with decreased clearance at higher doses. Fusidic acid is primarily eliminated by non-renal mechanisms, and a proportion of the drug is metabolised to seven or more breakdown products that can be detected in bile. Hypoalbuminaemia increases fusidic acid clearance, while clearance is decreased in the presence of severe cholestasis, and essentially unchanged in renal failure. Fusidic acid is highly protein-bound (91-98S), but has good penetration to a number of tissues including skin blisters, burns, infected bone and joints. Topical application of fusidic acid results in poor penetration through skin but good penetration into aqueous and vitreous humour. Little is known about the pharmacodynamics of fusidic acid, apart from the fact that it is slowly bactericidal against Staphylococcus aureus, and produces moderate post-antibiotic effects in vitro.