Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole and Dapsone and Their Hydroxylamine Metabolites
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 2
研究概览
简要总结
To determine the effects of fluconazole and either rifabutin or clarithromycin, alone and in combination, on the pharmacokinetics of first sulfamethoxazole-trimethoprim and then dapsone in HIV-infected patients.
Although prophylaxis for more than one opportunistic infection is emerging as a common clinical practice in patients with advanced HIV disease, little is known about possible adverse drug interactions. The need exists to define pharmacokinetics and pharmacodynamic adverse interactions of the many combination prophylactic regimens that may be prescribed.
详细描述
Although prophylaxis for more than one opportunistic infection is emerging as a common clinical practice in patients with advanced HIV disease, little is known about possible adverse drug interactions. The need exists to define pharmacokinetics and pharmacodynamic adverse interactions of the many combination prophylactic regimens that may be prescribed.
In Part A, patients receive sulfamethoxazole-trimethoprim (SMX/TMP) alone for 2 weeks, then in combination with fluconazole, rifabutin, or both drugs, each over 2-week periods in a randomly assigned order. Patients in Part B receive the same regimens except with clarithromycin substituted for rifabutin. In Part C, patients receive dapsone alone for 2 weeks, then in combination with fluconazole, rifabutin, or both drugs in the same manner as in Part A. Part D patients receive the same regimen as those in Part C, except with clarithromycin substituted for rifabutin. Patients are followed every 2 weeks.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Concurrent Medication:
- •Antiretroviral therapy provided patient has been on a stable dose for at least 4 weeks prior to study entry.
- •Methadone for drug abuse programs provided patient has been on a stable dose for at least 4 weeks prior to the study.
- •Patients must have:
- •HIV infection.
- •CD4 count >= 200 cells/mm
- •No active opportunistic infection.
- •Prior Medication:
- •Antiretroviral therapy.
- •Methadone for drug abuse therapy.
排除标准
- •Co-existing Condition:
- •Patients with the following symptoms or conditions are excluded:
- •Suspicion of gastrointestinal malabsorption problems (at discretion of investigator).
- •Known hypersensitivity to dapsone, SMX, or other sulfonamides, trimethoprim, clarithromycin, rifabutin or other rifamycins, fluconazole, or other azoles.
- •G-6-PD deficiency or methemoglobinemia (in Part C and D patients only).
- •Concurrent Medication:
- •Cytolytic agents.
- •Amiodarone.
- •Anesthetics, general.
- •Astemizole.
- •Azithromycin.
- •Barbiturates.
- •Carbamazepine.
- •Cimetidine.
- •Ciprofloxacin.
- •Cisapride.
- •Clarithromycin (except as required on study).
- •Clotrimazole.
- •Dexamethasone.
- •Disulfiram.
- •Erythromycin.
- •Fluoroquinolones.
- •Fluoxetine.
- •Gestodene.
- •Hydrochlorothiazide.
- •Hypoglycemics, oral.
- •Isoniazid.
- •Itraconazole.
- •Ketoconazole.
- •Levomepromazine.
- •Loratadine.
- •MAO inhibitors.
- •Methoxsalen.
- •Miconazole.
- •Nafcillin.
- •Narcotic analgesics.
- •Naringenin.
- •Nifedipine.
- •Norethindrone.
- •Pentazocine.
- •Phenothiazines.
- •Phenytoin.
- •Protease inhibitors.
- •Quinidine.
- •Ranitidine.
- •Rifabutin (except as required on study).
- •Rifampin.
- •Sedative hypnotics.
- •Sulfaphenazole.
- •Terfenadine.
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