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.
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- 適用できない
連絡先と場所
研究場所
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Washington
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Seattle、Washington、アメリカ、98195
- University of Washington, Clinical Research Center
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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)
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Tissue Raltegravir Concentrations
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Plasma Raltegravir Concentrations
時間枠：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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協力者と研究者
スポンサー
捜査官
- 主任研究者：Caroline Mitchell, MD、University Washington
- 主任研究者：Lisa Frenkel, MD、Seattle Children's Research Institute
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 38681-D
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
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