Levels of Raltegravir in the Female Genital Tissue
Modeling Intracellular and Extracellular Raltegravir (RAL) Pharmacokinetics in the Female Genital Tract and Blood After a Twice Daily 400mg Dose Over the Course of a Menstrual Cycle
This study is an investigation of the pharmacokinetics of raltegravir in the tissue of the female genital tract to determine if twice-daily dosing of 400mg achieves adequate drug levels to prevent viral integration of HIV-1. The study will also assess whether drug levels change in the tissue across the different phases of the menstrual cycle.
- Hypothesis #1: Twice daily dosing with raltegravir 400mg will result in intracellular concentrations that should be sufficient to suppress HIV-1 replication throughout the menstrual cycle.
- Hypothesis #2: Intracellular genital raltegravir peaks will be lower and troughs higher compared to extracellular concentrations in the plasma and PMBCs (peripheral blood mononuclear cells).
- Hypothesis #3: Intracellular raltegravir concentrations will be slightly lower during the luteal phase of the menstrual cycle due to cellular pumps such as p-glycoprotein, which are present in higher numbers during periods of high progesterone.
Descripción general del estudio
Descripción detallada
HIV-1 is shed in genital secretions which increase the risk of transmission between sexual partners and from mother to infant. Antiretroviral medication taken prior to exposure to HIV-1 can prevent viral transmission from a mother to her infant. Raltegravir (RAL), by blocking integration of viral cDNA into the host's genome, makes an excellent candidate for preventing HIV-1 infection. RAL is licensed for treatment with twice-daily dosing based on plasma trough concentrations; however, intracellular concentrations of RAL which are relevant to blocking infection of cells have not been previously studied. P-glycoprotein pumps, which are involved in regulating drug absorption and metabolism, can influence intracellular drug concentrations. P-glycoprotein concentrations appear to vary with menstrual cycle suggesting it may affect intracellular drug concentration of RAL in women.
Women will be enrolled in the study and followed during the course of a menstrual cycle while taking a dose of 400mg PO twice daily. An initial screening visit will be performed prior to enrollment and participation in the study. Review of medical history as well as blood and urine collection will occur during the screening visit. Once enrolled, participants will have blood and genital tract samples collected once a week for four weeks to assess intracellular concentrations of RAL in the blood and genital tract tissue.
Tipo de estudio
Inscripción (Actual)
Fase
- No aplica
Contactos y Ubicaciones
Ubicaciones de estudio
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Washington
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Seattle, Washington, Estados Unidos, 98195
- University of Washington, Clinical Research Center
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria
Volunteers must be:
- Over 18 years of age.
- Willing to abstain from sexual intercourse during course of study.
- Able to commit to follow-up visit schedule.
- Willing to abstain from use of vaginal medications or creams 48 hours prior to follow-up visits.
- Willing and able to provide informed consent.
Exclusion Criteria
Volunteers will not be eligible for the study if they:
- Are over 50 years of age.
- Are pregnant, attempting to become pregnant, or breast-feeding.
- Have irregular menstrual bleeding.
- Are using a hormonal form of birth control.
- Have abnormal liver/kidney function test results at screening visit.
- Have HIV-positive test result at screening visit.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: All
All patients were part of the intervention arm, as this was a pharmacokinetic study.
All women took Raltegravir 400mg orally, twice daily for 3 weeks.
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Dosage: 400mg/PO (by mouth) Frequency: Twice daily Duration: During course of menstrual cycle (28 days)
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Tissue Raltegravir Concentrations
Periodo de tiempo: 7, 14, 21 days
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Mean trough concentration from all three days.
Tissue concentrations are measured from cervical biopsy homogenate using a mass-spectroscopy-based method.
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7, 14, 21 days
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Plasma Raltegravir Concentrations
Periodo de tiempo: 7, 14, 21 days
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Mean trough concentration from all 3 days
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7, 14, 21 days
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Caroline Mitchell, MD, University Washington
- Investigador principal: Lisa Frenkel, MD, Seattle Children's Research Institute
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 38681-D
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