Fig 1.
CONSORT flow diagram describing volunteer enrolment, allocation to intervention, follow-up and analysis.
Fig 2.
Curves of geometric mean concentrations for the whole group.
(a) Total flucloxacillin concentrations, and (b) free flucloxacillin concentrations in the fed (■) and fasting state (●). Error bars are not shown since statistics were performed on paired differences.
Table 1.
Mean (95% CI) values for the pharmacokinetic parameters for total and free plasma flucloxacillin concentrations in the fed and fasting states, and ratiosa of fed/fasting (n = 12) based on non-compartmental analysis.
Table 2.
Population parameter values (95% CI) for free concentrations, modelled with Monolix using a one-compartment model with Tlag.
Fig 3.
Regression and residual plots of observed versus predicted concentrations in the fed (r = 0.96) and fasting (r = 0.97) states.
Weighted residuals represent the number of standard deviations by which each observation differs from the predicted value according to the normally distributed error model used.
Table 3.
Free flucloxacillin concentrations (geometric means) exceeded for 30%, 50% and 70% of 6- and 8-hour dose intervals in the fed and fasting states.
The ratio fed/fasting (geometric mean ± 90% CI) following 1000 mg oral flucloxacillin is also provided based on raw data, and modelled to steady-state.
Fig 4.
Probability of target attainment (PTA) for 30%, 50% and 70% of 6- and 8-hour dose intervals with flucloxacillin 1000 mg orally modelled to steady-state (one-compartment, first-order absorption with Tlag) for a range of MICs.
Serrated line: fed; continuous line: fasting. Relevant MIC90 of S. pyogenes (0.1 mg/L) and S. aureus (0.5 mg/L) are indicated by vertical serrated lines. Also shown is the MIC50 of S. aureus (0.25 mg/L).