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.
Visão geral do estudo
Descrição detalhada
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.
Tipo de estudo
Inscrição (Antecipado)
Estágio
- Fase 2
- Fase 1
Contactos e Locais
Contato de estudo
- Nome: Timothy Rawson, PhD
- Número de telefone: 0208 383 3231
- E-mail: tmr07@ic.ac.uk
Estude backup de contato
- Nome: Richard Wilson
- E-mail: r.wilson@imperial.ac.uk
Locais de estudo
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London, Reino Unido
- Recrutamento
- Imperial Clinical Research Facility
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Contato:
- Tim Rawson
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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).
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição cruzada
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Comparador Ativo: 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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Experimental: 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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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Measurement of total and unbound penicillin-V concentration
Prazo: 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
Prazo: 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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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Measurement of total and unbound probenecid concentration
Prazo: 45 minutes post an observed dose.
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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.
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Measurement of total and unbound probenecid concentration
Prazo: 180 minutes post an observed dose.
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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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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Timothy Rawson, PhD, Imperial College London
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Antecipado)
Conclusão do estudo (Antecipado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 21HH6936
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Prazo de Compartilhamento de IPD
Critérios de acesso de compartilhamento IPD
Tipo de informação de suporte de compartilhamento de IPD
- Protocolo de estudo
- Relatório de Estudo Clínico (CSR)
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