Influence of flucloxacillin treatment on plasma concentration of CYP - and UGT-substrate drugs.

Influence of flucloxacillin treatment on plasma concentration of CYP - and UGT-substrate drugs. - Flucloxacillin interaction study

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON56926

Enrollment

Registered

2024-07-26

Start date

2024-11-20

Completion date

Unknown

Last updated

2026-02-16

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

Conditions

infection Staphylococcus Aureus infection

Interventions

None listed

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: - Aged >=18 years - Treated with >=6 grams/24h flucloxacillin iv (or equivalent dose in case of renal impairment) for an intended duration of at least 10 days. - Concomitant treatment with at least one of the following substrate drugs at the moment of patient selection: diclofenac, metoprolol, oxycodone extended release tablet, pantoprazole or paracetamol. - Written informed consent.

Exclusion criteria

Exclusion criteria: - Concomitant use of specific CYP-, UGT- and P-gp inducers and inhibitors (see table S1 in the supplementary material of the study protocol). - Pregnancy - Dialysis patients - Dementia - IC-admission

Design outcomes

Primary

Measure	Time frame
Endpoint: The main study endpoint is the difference in AUC of each substrate drug (diclofenac, metoprolol, oxycodone, pantoprazole and paracetamol) between day 1/2 and day 10 (+/- 3 days) of flucloxacillin treatment. Parameter: Total substrate drug plasma concentration at specific time points (see section 7.3: study procedures).	—

Secondary

Measure	Time frame
Endpoints: - Difference in trough concentration of the substrate drugs between day 1/2 and day 10 (+/- 3 days) of flucloxacillin treatment. - Difference in trough concentration of substrate drug metabolites (4-OH diclofenac, alfa-OH-metoprolol, oxymorfon, noroxycodone, pantoprazole-sulfone, paracetamol-glucuronide) between day 1 and day 10 of flucloxacillin treatment. - Difference in AUC of substrate drug metabolites between day 1/2 and day 10 (+/- 3 days) of flucloxacillin treatment. - Difference in the ratio of the AUC of the substrate drugs and their metabolites between day 1/2 and day 10 (+/- 3 days) of flucloxacillin treatment. - Difference in the ratio of the trough concentration of the substrate drugs and their metabolites between day 1/2 and day 10 (+/- 3 days) of flucloxacillin treatment. - Difference in substrate drug dose between day 1/2 and day 10 (+/- 3 days) of flucloxacillin treatment. - Subgroup analysis of the above mentioned primary and secondary endpoints in groups of patients with specific CYP2C9 -, CYP2D6 -, CYP2C19 -, UGT1A1 - and UGT1A9 phenotypes (see supplementary material S2, table S2 for detailed information about the genotypes and corresponding phenotypes). Parameters CYP2C9 -, CYP2D6 -, CYP2C19 -, UGT1A1 - and UGT1A9 genotypes Gender Height Indication flucloxacillin treatment Substrate drug metabolite concentration in samples 1-3 at day 1/2 and day 10 (+/- 3 days) of flucloxacillin treatment (see section 7.3 study procedures). Age Weight Co-morbidities Co-medication (incl. dose) Flucloxacillin dose Substrate drug dose Total and unbound serum flucloxacillin concentration Unbound serum diclofenac and pantoprazole concentration Plasma creatinine Plasma ureum eGFR (CKD-EPI) Plasma CRP Plasma albumin Optional: plasma alpha-1-acid glycoprotein5 Plasma AST Plasma ALT Plasma ALP Plasma GGT Plasma Bilirubin Plasma LD Plasma triglyceride	—

Measure

Time frame

Endpoints: - Difference in trough concentration of the substrate drugs between day 1/2 and day 10 (+/- 3 days) of flucloxacillin treatment. - Difference in trough concentration of substrate drug metabolites (4-OH diclofenac, alfa-OH-metoprolol, oxymorfon, noroxycodone, pantoprazole-sulfone, paracetamol-glucuronide) between day 1 and day 10 of flucloxacillin treatment. - Difference in AUC of substrate drug metabolites between day 1/2 and day 10 (+/- 3 days) of flucloxacillin treatment. - Difference in the ratio of the AUC of the substrate drugs and their metabolites between day 1/2 and day 10 (+/- 3 days) of flucloxacillin treatment. - Difference in the ratio of the trough concentration of the substrate drugs and their metabolites between day 1/2 and day 10 (+/- 3 days) of flucloxacillin treatment. - Difference in substrate drug dose between day 1/2 and day 10 (+/- 3 days) of flucloxacillin treatment. - Subgroup analysis of the above mentioned primary and secondary endpoints in groups of patients with specific CYP2C9 -, CYP2D6 -, CYP2C19 -, UGT1A1 - and UGT1A9 phenotypes (see supplementary material S2, table S2 for detailed information about the genotypes and corresponding phenotypes). Parameters CYP2C9 -, CYP2D6 -, CYP2C19 -, UGT1A1 - and UGT1A9 genotypes Gender Height Indication flucloxacillin treatment Substrate drug metabolite concentration in samples 1-3 at day 1/2 and day 10 (+/- 3 days) of flucloxacillin treatment (see section 7.3 *study procedures*). Age Weight Co-morbidities Co-medication (incl. dose) Flucloxacillin dose Substrate drug dose Total and unbound serum flucloxacillin concentration Unbound serum diclofenac and pantoprazole concentration Plasma creatinine Plasma ureum eGFR (CKD-EPI) Plasma CRP Plasma albumin Optional: plasma alpha-1-acid glycoprotein5 Plasma AST Plasma ALT Plasma ALP Plasma GGT Plasma Bilirubin Plasma LD Plasma triglyceride

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Countries

Netherlands

Outcome results