Effect of ibuprofen on the pharmacokinetics of intravenous flucloxacillin in healthy adults
- Author(s)
- Boast, A; Legg, A; McCarthy, J,; Roberts, JA; Tong, S YC; Duffull, S; Gwee, A;
- Journal Title
- International Journal of Antimicrobial Agents
- Publication Type
- Dec 1
- Abstract
- BACKGROUND: Ibuprofen is frequently co-administered with antibiotics for its analgesic effect when treating infections. In vitro studies have shown ibuprofen exhibits concentration-dependent inhibition of the organic anion transporters (OAT) 1 and OAT3 and therefore may reduce the clearance of β-lactams including flucloxacillin, in a similar manner to probenecid. We therefore aimed to evaluate the effect of ibuprofen on the pharmacokinetics (PK) of flucloxacillin in healthy volunteers. METHODS: Single site, PK study of 10 healthy adult volunteers. Over a three-day intervention period, participants received intravenous (IV) flucloxacillin 2000 mg twice daily with oral ibuprofen 400 mg twice daily on days 2 and 3. Total and unbound flucloxacillin plasma concentrations were collected at predefined time points. A population PK model was developed using a non-linear mixed effects modelling approach and ibuprofen assessed as a covariate in the final model. RESULTS: Ten participants with a median age of 24.4 years (range 18.8-54.5) and weight of 68.3 kilograms (range 50.5-85.7) were included. A median of 51.5 (range 34-52) samples were collected per participant. The final two-compartment model included saturable protein binding and allometric scaling of weight on clearance. Ibuprofen was not found to be a significant covariate on K(d) (binding dissociation constant), B(max) (maximum binding capacity) or clearance. CONCLUSION: Orally administered ibuprofen had no measurable effect on plasma flucloxacillin PK in healthy adults. Given the lack of drug-drug interaction, there is no benefit to prescribe ibuprofen alongside flucloxacillin to increase flucloxacillin exposure.
- Publisher
- Elsevier
- Keywords
- anti-bacterial agents; beta-lactam; floxacillin; healthy volunteers; pharmacokinetics
- Research Division(s)
- Infection and Global Health
- PubMed ID
- 41338520
- Publisher's Version
- https://doi.org/10.1016/j.ijantimicag.2025.107684
- Open Access at Publisher's Site
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Creation Date: 2025-12-15 09:43:16
Last Modified: 2025-12-15 09:43:25