Effect of food on oral flucloxacillin pharmacokinetics and pharmacodynamics in healthy volunteers

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12617001046392

Enrollment

Registered

2017-07-18

Start date

2014-03-01

Completion date

2014-04-03

Last updated

2017-08-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

Flucloxacillin is usually recommended to be given on an empty stomach, because food reduces and delays peak concentrations. It is now known that for penicillins, the time the free (unbound) concentrations are above the minimum inhibitory concentrations is more important for bacterial kill than peak concentrations. In this study, the effects of food on flucloxacillin PK-PD were assess using a modern assay to accurately quantify free flucloxacillin concentrations. Total and free flucloxacillin concentrations were measured for 12 hours after a single oral dose of flucloxacillin 1000 mg, after a standardized breakfast and in a fasting state separated by a week's washout. Pharmacokinetics and pharmacodynamics were compared in the fed and fasting states. Food reduced the total and free flucloxacillin area under the curve by about 20%, and the peak by about 50%, and increased the time to reach peak concentrations by approximately 2-fold. These changes did not importantly impact on parameters such as free time above MIC and probability of target attainment suggesting that flucloxacillin can be taken with food without compromising efficacy in most cases.

Interventions

Volunteers received flucloxacillin 1000 mg orally on an empty stomach or after a standardized high-fat high-calorie breakfast (per FDA recommendations for bioequivalence studies ie. equating to ~968 kcal of energy, 38 g of protein, 65 g of fat and 58 g of carbohydrate) after an 8 hour overnight fast (free access to water during this time) on two study days separated by a 7-day 'washout period'.

Study design

Allocation

Non-randomised trial

Primary purpose

Treatment

Masking

Open (masking not used)

Eligibility

Sex/Gender

All

Age

18 Years to 40 Years

Healthy volunteers

Yes

Inclusion criteria

Healthy volunteers

Exclusion criteria

Food intolerance, pregnancy, chronic illness, renal impairment (creatinine clearance < 80 mL/min by Cockcroft-Gault formula), liver dysfunction, malabsorption or known intolerance of flucloxacillin. Volunteers were excluded from the study if they took any regular medications (other than a hormonal oral contraceptive pill) or were intolerant of fasting for up to 10 hours.

Outcome results