PubMed · 4822311
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O Garborg. 1974-02-25. [Fucidin].. https://pubmed.ncbi.nlm.nih.gov/4822311/
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OBJECTIVE: Fusidic acid with rifampicin is used for the treatment of severe staphylococcal infection, particularly prosthetic joint infections. Previous studies using twice daily fusidic acid showed rifampicin increases fusidic acid clearance, potentially causing sub-therapeutic concentrations. It is uncertain whether this occurs with three-times daily dosing. This study sought to re-evaluate this potential drug-drug interaction. METHODS: In this prospective, open-label drug-drug interaction population pharmacokinetic (PK) study, participants were randomized to receive fusidic acid or rifampicin for 24 hours, followed by combination therapy for the duration of treatment. Drug concentration assays used liquid-chromatography mass spectroscopy on dried blood spots. Population PK models were built for fusidic acid, rifampicin and 25-desacetyl rifampicin. RESULTS: Ten participants were recruited. Inter-individual variability for both absorption (98.1%) and clearance (77.8%) were high for fusidic acid. A population pharmacokinetic model for fusidic acid revealed that early autoinhibition dominated over later rifampicin-mediated induction, resulting in a net decrease in fusidic acid clearance. The mean fusidic acid area under the curve during each dosing interval (AUCτ) at steady state was 1.76-fold [0.049, 34.918] higher relative to Day 1, despite high uncertainty.Large inter-individual (110%) variability in absorption was observed for rifampicin. There was no apparent effect on rifampicin metabolism by fusidic acid co-administration, however, fusidic acid decreased clearance of 25-desacetyl rifampicin. CONCLUSION: In patients treated with fusidic acid three times daily in combination with rifampicin, autoinhibition potentially counteracted rifampicin induction such that fusidic acid concentrations were not reduced. Rifampicin clearance was not affected by fusidic acid, but 25-desacetyl rifampicin clearance was decreased. There was large inter-individual variability in the observed concentrations and final parameter estimates.
22 HIV-positive homosexual men were treated with fusidic acid tablets (500 mg t.i.d.) for a period of 2-12 months (mean 71/2). At entry, all had a CD4-count less than 500 X 10(6)/l, and/or a pokeweed mitogen lymphocyte proliferation response of less than 50% of 2 normal controls, and no overt opportunistic infections. No significant immunological changes were observed and no definite beneficial clinical effect. On the 10th-13th day of treatment, 12 of the patients developed fever and an itchy exanthema. The symptoms disappeared spontaneously in 9 patients. No hematological or biochemical side effects were seen. Thus, in this pilot study of fusidic acid therapy of HIV-infected men, no significant effect could be detected.
The effect of fusidic acid on the multiplication of human immunodeficiency virus in monocyte-derived macrophages was examined in in vitro cultures. Virus titers, measured by reverse transcriptase and by p24 antigen in the supernatants and in lysed cells, were reduced in some experiments by 50 micrograms/ml or more; in other experiments, 10 micrograms of fusidic acid per ml added to the cells simultaneously with the virus inoculation reduced virus titers. The effect was comparable in peripheral blood lymphocytes. The drug was generally toxic to the cells, both macrophages and peripheral blood lymphocytes, in concentrations of 50 micrograms/ml or more.