Addition of Probenecid to Penicillin-V Therapy (ADDPROPEN)
Addition of Probenecid to Penicillin-V Therapy: an Open Label, Cross-over Study in Healthy Volunteers
This study aims to build on previous work characterising the PK of penicillin-V to explore the potential impact of probenecid on PK-PD target attainment. Achievement of the aims of this study would provide data to support the design of experimental studies exploring the clinical impact of probenecid on treatment outcomes and also provide a rationale for exploration of probenecid's effects on a larger number of beta-lactam antibiotics.
Hypothesis: Addition of probenecid to oral phenoxymethylpenicillin (penicillin-V) has a clinically relevant effect on pharmacokinetic-pharmacodynamic (PK-PD) target attainment.
연구 개요
상세 설명
Participants will be screened and consented to attend Imperial College Clinical Research Facility (CRF) at Hammersmith Hospital on two study visits, at least 7 days apart. For one visit (randomised), participants will be required to take penicillin-V only. For their other visit, they will take penicillin-V plus probenecid at standard recommended dose. Prior to the study visits, participants may be required to have taken 36-hours of penicillin +/- probenecid, documenting this in a dosing diary. On arrival at the CRF, the participant will take an observed dose of penicillin +/- probenecid. They will undergo blood draw via needle phlebotomy or a cannula (participant choice) at 45 and 180 minutes post the observed. Samples will be spun down and frozen at -80oC. They will subsequently be analysed using an in-house HPLC-MS/MS methodology to determine total and free-unbound drug concentration.
For analysis, data from this study will be pooled with rich PK data from a prior study that assessed plasma concertation of penicillin-V in healthy volunteers. Pmetrics in R will be used to model the data looking to explore the effect of probenecid on clearance of free-penicillin-V. Probability of target attainment for streptococci species will also be estimated to evaluate the potential clinical impact of the addition of probenecid to routine penicillin-V use. Rich PK data for intravenous benzylpenicillin will be used to estimate PK-PD target attainment and PTAs for intravenous formulations, allowing direct comparison of oral and IV regimes.
연구 유형
등록 (예상)
단계
- 2 단계
- 1단계
연락처 및 위치
연구 연락처
- 이름: Timothy Rawson, PhD
- 전화번호: 0208 383 3231
- 이메일: tmr07@ic.ac.uk
연구 연락처 백업
- 이름: Richard Wilson
- 이메일: r.wilson@imperial.ac.uk
연구 장소
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London, 영국
- 모병
- Imperial Clinical Research Facility
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연락하다:
- Tim Rawson
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Adult healthy volunteers (>18 years old).
- Previously taken penicillin-based antibiotics without allergic response.
- Estimated Glomerular Filtration Rate (eGFR) > 90.
Exclusion Criteria:
- Lacking capacity to consent.
- Documented allergy to penicillin, other beta-lactam antibiotics, or probenecid.
- History of G6PD Deficiency.
- Known blood dyscrasias.
- Anaemia (Hb < 12g/dL female, 13g/dL males).
- Abnormal liver function (ALT, AST, ALP or bilirubin > ULN).
- eGFR < 90.
- Pregnant or likely to become pregnant during study period.
- Breastfeeding women.
- Symptoms consistent with active infection.
- History of gout or uric acid kidney stones.
- Taking regular medication that may interact with probenecid including, but not limited to methotrexate, lorazepam, acetaminophen, oral hypoglycaemic medication, sulfa containing drugs, non-steroidal anti-inflammatory drugs.
- History of evidence of any medical, neurological, or psychological condition that would expose the subject to an undue risk of a significant adverse event or interfere with study assessments during the course of the trial as determined by the clinical judgement of the investigator.
- Recent involvement in other research (within prior 3 months).
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 크로스오버 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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활성 비교기: Penicillin alone
Penicillin orally at dose of either 250mg, 500mg, 750mg QDS for 36 hours.
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Addition of 500mg QDS to oral penicillin.
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실험적: Penicillin plus probenecid
Penicillin orally at dose of either 250mg, 500mg, 750mg QDS for 36 hours. PLUS Probenecid 500mg QDS for 36 hours. |
Addition of 500mg QDS to oral penicillin.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Measurement of total and unbound penicillin-V concentration
기간: 45 minutes post an observed dose.
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Measurement of blood concentration at 45 minutes post dose with and without probenecid.
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45 minutes post an observed dose.
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Measurement of total and unbound penicillin-V concentration
기간: 180 minutes post an observed dose.
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Measurement of blood concentration at 180 minutes post dose with and without probenecid.
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180 minutes post an observed dose.
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Measurement of total and unbound probenecid concentration
기간: 45 minutes post an observed dose.
|
Measurement of blood concentration at 45 minutes post observed penicillin-V dose with and without probenecid.
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45 minutes post an observed dose.
|
|
Measurement of total and unbound probenecid concentration
기간: 180 minutes post an observed dose.
|
Measurement of blood concentration at 180 minutes post observed penicillin-V dose with and without probenecid.
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180 minutes post an observed dose.
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공동 작업자 및 조사자
수사관
- 수석 연구원: Timothy Rawson, PhD, Imperial College London
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (예상)
연구 완료 (예상)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
기타 연구 ID 번호
- 21HH6936
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
IPD 공유 기간
IPD 공유 액세스 기준
IPD 공유 지원 정보 유형
- 연구 프로토콜
- 임상 연구 보고서(CSR)
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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