In healthy volunteers, taking flucloxacillin with food does not compromise effective plasma concentrations in most circumstances

Abstract

It is usually recommended that flucloxacillin is given on an empty stomach. The aim of this study was to compare total and free flucloxacillin concentrations after oral flucloxacillin, given with and without food, based on contemporary pharmacokinetic and pharmacodynamic targets. Flucloxacillin 1000 mg orally was given to 12 volunteers, after a standardised breakfast and while fasting, on two separate occasions. Flucloxacillin concentrations over 12 hours were measured by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters, and pharmacodynamic endpoints related to target concentration achievement, were compared in the fed and fasting states. For free flucloxacillin, the fed/fasting area under the concentration-time curve from zero to infinity (AUC0-∞) ratio was 0.80 (p<0.01, 90% CI 0.70–0.92), the peak concentraton (Cmax) ratio 0.51 (p<0.001, 0.42–0.62) and the time to peak concentration (Tmax) ratio 2.2 (p<0.001, 1.87–2.55). The ratios for total flucloxacillin concentrations were similar. The mean (90% CI) fed/fasting ratios of free concentrations exceeded for 30%, 50% and 70% of the first 6 hours post-dose were 0.74 (0.63–0.87, fed inferior p<0.01), 0.95 (0.81–1.11, bioequivalent) and 1.15 (0.97–1.36, fed non-inferior), respectively. 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. Overall, this study shows that food reduced the AUC0-∞ and Cmax, and prolonged the Tmax of both free and total flucloxacillin concentrations compared with the fasting state, but achievement of free concentration targets associated with efficacy was in most circumstances equivalent. These results suggest that taking flucloxacillin with food is unlikely to compromise efficacy in most circumstances.

Flucloxacillin bone and soft tissue concentrations assessed by microdialysis in pigs after intravenous and oral administration

“… 38 This leads us to believe that the primary reason for the low PO concentrations in the present study is reduced absorption from the intestine, because of the use of general anaesthesia. However, free human plasma C max observed by Gardiner et al 22 complies well with the observed plasma C max in the present experimental porcine model and therefore, indirectly, suggests otherwise.…”

“…For flucloxacillin, S. aureus exhibits MIC values in the range of 0.12 μg/ml to 2 μg/ml, 3 and it remains a matter of further research to decide which target to employ. 21 , 22 Moreover, the definition of sufficient f T > MIC remains a matter of dispute. For perioperative prophylaxis, the conventional recommendation is to achieve 100% f T > MIC throughout surgery, whereas for antibiotic therapy of, for example, chronic osteomyelitis, the literature suggests that 50% f T > MIC may be sufficient for β-lactam antibiotic therapeutic effect.…”

Oral Flucloxacillin for Treating Osteomyelitis: A Narrative Review of Clinical Practice

“…It is likely that oral FLU could also be associated with such an interaction, although possibly at a subclinical level. Contrary to common belief, it is probably not necessary to administer oral FLU on an empty stomach, as concomitant food intake does not appear to alter the pharmacokinetic parameters (56). One other interaction of note is that combining treated with FLU (like other penicillins) with probenecid commonly can boost the serum FLU concentrations (8,40,42).…”

When should I take my medicines?

“…A recent study13 reviewed pharmacokinetic data for flucloxacillin and found that food decreased total flucloxacillin concentrations. However, concentrations of free flucloxacillin that are associated with efficacy were obtained in most circumstances.…”