Effect of probenecid or ibuprofen on flucloxacillin exposure in healthy adults
Effect of pharmacokinetic enhancers on flucloxacillin serum and urinary concentrations in healthy adults
University of Melbourne
20 participants
Jan 29, 2024
Interventional
Conditions
Summary
Flucloxacillin is the treatment of choice for proven or suspected Methicillin-susceptible Staphylococcus aureus (MSSA) infections in Australian Therapeutic Guidelines. However, it needs to be given at least four times a day, which can be difficult for patients to adhere to. In this study, we would like to determine whether the use of probenecid or ibuprofen can reduce flucloxacillin dosing frequency. Healthy adult volunteers will be enrolled into two parallel groups (10 people in each group), and prescribed probenecid or ibuprofen, in combination with flucloxacilin.
Eligibility
Inclusion Criteria5
- Body mass index (BMI) of 18.0 – 32.0 kg/m2 and body weight >= 50.0 kg.
- Medically healthy, determined by medical history, physical examination, non-clinically significant laboratory profiles, vital signs, and 12-lead ECG at screening, as deemed by the Investigator.
- Females must be non-pregnant, non-lactating, or postmenopausal for at least 1 year or surgically sterile for at least 6 months prior to dosing.
- If relevant, non-pregnant female participants will be required to use an effective form of contraception from 28 days prior to the study until the end of study.
- Males must not have a pregnant partner and must agree to use condoms as a method of contraception from the time of signing informed consent until the end of study.
Exclusion Criteria5
- History of any clinically important cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal, or other major disease, as determined by the Investigator.
- Significant history of hospitalization for illness within the six months prior to enrolment into the study, or major surgery within the 12 months prior to enrolment into the study, as assessed by the study physician or investigator.
- A contraindication or significant risk associated with the use of either of IMPs.
- Likely to have altered drug exposures.
- Other health risks as determined by the study physician.
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Interventions
The intervention occurs at the Doherty Clinical Trial unit. Investigational Medicinal Products (IMPs)--flucloxacillin and probenecid—will be administered by registered nurses (Div 1, APRAH) and/or other medical staff listed in the Delegation of Responsibilities Log, unless stated otherwise. This is a non-randomized study. Participants can choose which group they want to be in, either Group 1 or Group 2, until each group is full. Group 1. During the 6-day intervention period, participants will be prescribed flucloxacillin and probenecid at various doses, as well as with various durations and modes of administration, as follows. Day 1. 1 g of flucloxacillin capsule, orally, four times (6 hours apart)--first dose will be administered at Doherty Clinical Trial unit, while the other 3 doses will be administered at home and participants will be provided the required number of capsules and one extra dose in a take-home pack; Day 2. 1 g of flucloxacillin capsule, orally, one time; Day 3. 2 g of flucloxacillin, intravenous infusion (IV), one time; Day 4. Washout (no IMP is prescribed); Day 5. 1 g of flucloxacillin capsule and 500 mg of probenecid tablet, orally, three times (8 hours apart); Day 6. 1 g of flucloxacillin capsule and 500 mg of probenecid tablet, orally, one dose (8 hours after the last dose on Day 5). Blood sampling is to occur before and after doses, except during the washout period. Urine sampling is after the dose, except for Day 1 and 4.
Locations(1)
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ACTRN12623001155684