Effect of ibuprofen on the pharmacokinetics of intravenous flucloxacillin in healthy adults

Boast, A; Mccarthy, J; Legg, A; Tong, SY; Roberts, JA; Duffull, S; Gwee, A

Author(s): Boast, A; Mccarthy, J; Legg, A; Tong, SY; Roberts, JA; Duffull, S; Gwee, A;
Details: Publication Year 2026-02,Volume 67,Issue #2,Page 107684
Journal Title: International Journal of Antimicrobial Agents
Abstract: OBJECTIVE: Ibuprofen is frequently co-administered with antibiotics for its analgesic effect when treating infections. In vitro studies have shown that ibuprofen exhibits concentration-dependent inhibition of organic anion transporters (OAT) 1 and OAT3, and therefore may reduce clearance of beta-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: A single-site PK study of 10 healthy adult volunteers was carried out. Over a 3-d 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 was assessed as a covariate in the final model. RESULTS: Ten participants with a median age of 24.4 y (range 18.8-54.5 y) and median weight of 68.3 kg (range 50.5-85.7 kg) were included. A median of 51.5 (range 34-52) samples was 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 prescribing ibuprofen alongside flucloxacillin to increase flucloxacillin exposure.
Publisher: Elsevier
Keywords: Humans; *Ibuprofen/administration & dosage/pharmacology/pharmacokinetics; Adult; *Anti-Bacterial Agents/pharmacokinetics/administration & dosage; *Floxacillin/pharmacokinetics/administration & dosage; Male; Healthy Volunteers; Middle Aged; Female; Young Adult; Drug Interactions; Adolescent; Administration, Intravenous; Administration, Oral; Antibacterial agents; Floxacillin; Pharmacokinetics; beta-lactam
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: https://doi.org/10.1016/j.ijantimicag.2025.107684
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-12-15 09:43:16

Last Modified: 2026-04-30 10:18:57