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

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 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

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.