ArticleAntimicrobial agents and chemotherapy2013
Population pharmacokinetics of fusidic acid: rationale for front-loaded dosing regimens due to autoinhibition of clearance.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- A prospective pharmacokinetic interaction study between rifampicin and fusidic acid for the treatment of staphylococcal infections.The Journal of antimicrobial chemotherapy · 2026Trial
- Population Pharmacokinetics and Target Attainment of Meropenem in Plasma and Tissue of Morbidly Obese Patients after Laparoscopic Intraperitoneal Surgery.Antimicrobial agents and chemotherapy · 2015Trial
- Population Pharmacokinetic Modeling of the Enterohepatic Recirculation of Fimasartan in Rats, Dogs, and Humans.The AAPS journal · 2015Trial
- Repurposing fusidic acid as an antimicrobial against enterococci with a low probability of resistance development.International microbiology : the official journal of the Spanish Society for Microbiology · 2024Article
- Population pharmacokinetic rationale for intravenous contezolid acefosamil followed by oral contezolid dosage regimens.Antimicrobial agents and chemotherapy · 2024Article
- Comprehensive stability analysis of 13 β-lactams and β-lactamase inhibitors inAntimicrobial agents and chemotherapy · 2024Article
- Population pharmacokinetics and humanized dosage regimens matching the peak, area, trough, and range of amikacin plasma concentrations in immune-competent murine bloodstream and lung infection models.Antimicrobial agents and chemotherapy · 2024Article
- Improved characterization of aminoglycoside penetration into human lung epithelial lining fluid via population pharmacokinetics.Antimicrobial agents and chemotherapy · 2024Article
- Central and peripheral lung deposition of fluticasone propionate dry powder inhaler formulations in humans characterized by population pharmacokinetics.Pharmaceutical research · 2023Article
- Polymyxin B and fusidic acid, a novel potent synergistic combination againstFrontiers in microbiology · 2023Article
- Pharmacokinetic and Biochemical Profiling of Sodium Dichloroacetate in Pregnant Ewes and Fetuses.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Comparable Bioavailability and Disposition of Pefloxacin in Patients with Cystic Fibrosis and Healthy Volunteers Assessed via Population Pharmacokinetics.Pharmaceutics · 2019Article
- Novel Population Pharmacokinetic Approach to Explain the Differences between Cystic Fibrosis Patients and Healthy Volunteers via Protein Binding.Pharmaceutics · 2019Article
- Generating Robust and Informative NonclinicalAntimicrobial agents and chemotherapy · 2019Review
- Pharmacokinetic-pharmacodynamic modelling to investigate in vitro synergy between colistin and fusidic acid against MDR Acinetobacter baumannii.The Journal of antimicrobial chemotherapy · 2019Article
- Four Decades of β-Lactam Antibiotic Pharmacokinetics in Cystic Fibrosis.Clinical pharmacokinetics · 2019Review
- Clinical Regimens of Favipiravir Inhibit Zika Virus Replication in the Hollow-Fiber Infection Model.Antimicrobial agents and chemotherapy · 2018Article
- Activities of Combinations of Antistaphylococcal Antibiotics with Fusidic Acid against Staphylococcal Biofilms inAntimicrobial agents and chemotherapy · 2018Article
- Zika Virus Replication Is Substantially Inhibited by Novel Favipiravir and Interferon Alpha Combination Regimens.Antimicrobial agents and chemotherapy · 2018Article
- The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections.Intensive care medicine · 2017Review
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The objectives of this analysis were to develop a population pharmacokinetic (PK) model to describe the absorption and disposition of fusidic acid after single and multiple doses and to determine the effect of food on the rate and extent of bioavailability. Plasma PK data from three phase 1 studies (n = 75; n = 14 with and without food) in which healthy subjects received sodium fusidate (500 to 2,200 mg) as single or multiple oral doses every 8 h (q8h) or q12h for up to 7 days were modeled using S-ADAPT (MCPEM algorithm). Accumulation of fusidic acid after multiple doses was more than that predicted based on single-dose data. The PK of fusidic acid was best described using a time-dependent mixed-order absorption process, two disposition compartments, and a turnover process to describe the autoinhibition of clearance. The mean total clearance (% coefficient of variation) was 1.28 liters/h (33%) and the maximum extent of autoinhibition was 71.0%, with a 50% inhibitory concentration (IC(50)) of 46.3 mg/liter (36%). Food decreased the extent of bioavailability by 18%. As a result of the autoinhibition of clearance, steady state can be achieved earlier with dosing regimens that contain higher doses (after 8 days for 750 mg q12h and 1 day for 1,500 mg q12h on day 1 followed by 600 mg q12h versus 3 weeks for 500 mg q12h). Given that large initial doses autoinhibit the clearance of fusidic acid, this characteristic provides a basis for the administration of front-loaded dosing regimens of sodium fusidate which would allow for effective concentrations to be achieved early in therapy.
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