Relevant MIC 90 of S. Also shown is the MIC 50 of S. This study in volunteers investigated the impact of a standardized, high-fat, high-calorie meal on free flucloxacillin pharmacokinetics, using a sensitive assay, over the full concentration-time curve and with regard to contemporary pharmacodynamic targets.
Flucloxacillin taken with food was associated with a significant reduction in free and total AUC and C max , and a prolonged T max , as shown with total flucloxacillin concentrations in previous studies [ 5 , 6 ]. These effects resulted from a decrease in oral availability, a longer T lag and a lower k a.
Differences in achievement of pharmacodynamic targets were minor and ranged from a small reduction in PTA for a free concentration target of greater than 0.
These results have important implications for clinical practice as they provide a scientific basis for reconsidering the recommendation that flucloxacillin should always be administered on an empty stomach.
For this patient group, bacteriostasis is probably all that is necessary. For the small subpopulation of patients infected with a strain of S. It is often difficult to determine whether skin and soft tissue infections such as cellulitis are caused by S. In either case the MIC of the pathogen is rarely known, so that the most certain approach in these conditions may be to recommend administration on an empty stomach. Nevertheless, this potential gain in a small proportion of cases must be balanced against the difficulty that many patients experience in remembering to take flucloxacillin an hour before meals and the likelihood of missed doses, which may have a much greater effect on the clinical efficacy.
Additionally, if it was clinically important to reach a bactericidal target for all potentially infecting S. In these situations, oral flucloxacillin in doses of mg 6-hourly, irrespective of whether it is taken with food or in the fasting state, may fail to achieve adequate therapeutic targets for many strains and an alternative treatment strategy should be considered. An increase in the oral flucloxacillin dose beyond mg or dosing frequency e.
This supports results from other volunteer studies [ 23 ]. The results were modelled for both 6- and 8-hourly dosing, as both regimens have been recommended, and because in practice it is almost impossible to dose precisely every 6 hours. At the least it is likely that there will be an 8-hour delay while the patient sleeps.
There are several limitations to this study. It was conducted with a fixed dose of mg of flucloxacillin in young, healthy volunteers with a relatively normal BMI and normal renal function. In practice, flucloxacillin is administered to patients with a wide range of age, BMI, and renal function [ 24 — 26 ]. Patients with impaired clearance of flucloxacillin will have an increase in the PTA, both with and without food, and this may increase the chance of therapeutic success. Additionally, the food given to the volunteers was a high-fat, high-calorie meal, and this may be larger than that usually consumed by patients.
Any effect of administration with meals in clinical practice may well be less than demonstrated here with volunteers. We have not investigated the effect of food on doses of flucloxacillin other than mg, but it is likely that the effect would be similar.
Finally, the steady-state data rests on the validity of the one compartment model with T lag and first-order absorption. Because of the uncertainty of translating these findings into clinical practice it would be useful to study pharmacodynamic target attainment of flucloxacillin concentrations in the variety of clinical settings in which oral flucloxacillin is prescribed.
These findings in adults may not translate directly into the paediatric population and this would be worthy of further study given that oral administration of flucloxacillin is particularly difficult in children [ 27 ].
Finally, it should not be assumed that the findings of this study extend to other isoxazolyl penicillins, but this too warrants further investigation. Contrary to what has been widely accepted since the s, the results of this study indicate that taking flucloxacillin with food may not compromise effective flucloxacillin plasma concentrations in most circumstances.
Other potential advantages of taking flucloxacillin with food include convenience, improved compliance and reduction in adverse effects such as nausea. Rather than focusing on administration on an empty stomach, it is more important that dosing is individualized according to known or suspected susceptibility to flucloxacillin, illness severity, and host characteristics.
The findings of this study have significant implications for dosing of oral flucloxacillin worldwide. For comparision with Fig 4 in paper. National Center for Biotechnology Information , U.
PLoS One. Published online Jul Sharon J. Philip G. Jared K. Heather L. Richard J. Stephen T. Evan J. Jacobus P. Author information Article notes Copyright and License information Disclaimer. Competing Interests: The authors have declared that no competing interests exist. Received Feb 16; Accepted Apr This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
This article has been cited by other articles in PMC. Associated Data Supplementary Materials S1 Dataset: Raw flucloxacillin urine concentration results fed versus fasting. S2 Dataset: Likelihood results for various combinations of T lag versus no T l ag and first- versus zero-order. S3 Dataset: Results for zero-order elimination.
S1 Fig: For comparison with Fig 4 in the manuscript, which is also included below as a reference. S1 File: Study protocol. Abstract It is usually recommended that flucloxacillin is given on an empty stomach. Introduction Flucloxacillin is used in many parts of the world for treating infections due to methicillin- susceptible Staphylococcus aureus and Streptococcus pyogenes.
Modelling Prediction of steady-state free concentrations was carried out as follows. Results The 12 participants 5 female, 7 male had a mean range age of 26 21—38 years, weight of 74 54—96 kg and height of — cm. Open in a separate window. Fig 1. Non-compartmental pharmacokinetic analysis Plasma concentration-time curves for geometric mean total and free flucloxacillin for the fed and fasting states are plotted in Fig 2. Fig 2. Curves of geometric mean concentrations for the whole group.
Pharmacokinetic and pharmacodynamic modelling A two-compartment model was excluded because of no suggestive visual evidence in the individual concentration-time curves, and by higher values for the Akaike information criteria AIC compared with a one-compartment model using PKSolver. Fig 3. Fig 4. Discussion This study in volunteers investigated the impact of a standardized, high-fat, high-calorie meal on free flucloxacillin pharmacokinetics, using a sensitive assay, over the full concentration-time curve and with regard to contemporary pharmacodynamic targets.
Clinical implications These results have important implications for clinical practice as they provide a scientific basis for reconsidering the recommendation that flucloxacillin should always be administered on an empty stomach.
Limitations There are several limitations to this study. Flucloxacillin is an antibiotic used to treat bacterial infections, such as ear infections and skin infections including cellulitis. It works by killing or stopping the growth of bacteria bugs. Flucloxacillin belongs to a group of antibiotics called penicillins. Like all antibiotics, flucloxacillin is not effective against infections caused by viruses.
In New Zealand, flucloxacillin is available as capsules and liquid and can be given as an injection in the hospital. Flucloxacillin is best taken on an empty stomach, one hour before eating food.
This is because your body may absorb less flucloxacillin after a meal, making it less effective. Like all medicines, flucloxacillin can cause side effects, although not everyone gets them. Often side effects improve as your body gets used to the new medicine.
Flucloxacillin may interact with a few medications and herbal supplements, so check with your doctor or pharmacist before starting flucloxacillin or before starting any new medicines.
If you are taking the contraceptive 'pill', the effectiveness of the 'pill' can be reduced if you have a bout of being sick vomiting or diarrhoea which lasts for more than 24 hours. If this happens, ask your doctor or pharmacist for advice about contraception over the following few days.
The content on this page will be of most use to clinicians, such as nurses, doctors, pharmacists, specialists and other healthcare providers. Looking for Where to get medical help A health professional or service Patient portals Newsletters View all. What is flucloxacillin?
Dose The dose of flucloxacillin will be different for different people depending on the type of infection and your age. Adults : the usual dose is mg or mg three or four times a day. Children : the dose for children will depend on their body weight. It is usually given 4 times a day.
Your doctor will advise you on how long to take flucloxacillin for usually 5 to 7 days. Always take your flucloxacillin exactly as your doctor has told you. The pharmacy label on your medicine will tell you how much to take, how often to take it, and any special instructions. How to take flucloxacillin Flucloxacillin is best taken on an empty stomach, one hour before eating food. Results for 8 hours post-dose and those predicted for steady state were similar.
Comparison of probability of target attainments for fed versus fasting across a range of minimum inhibitory concentrations MICs were in line with these results. These results suggest that taking flucloxacillin with food is unlikely to compromise efficacy in most circumstances. Abstract It is usually recommended that flucloxacillin is given on an empty stomach.
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