The Pharmacokinetic Interaction Between Metformin and Nizatidine in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Composite of Pharmacokinetics of co-administration of nizatidine & metformin in healthy volunteers.
研究概览
简要总结
This study will address the following question: Does nizatidine affect the pharmacokinetics of metformin in healthy volunteers? Recent studies in the Giacomini laboratory have indicated that nizatidine may block metformin elimination from the kidney by inhibiting organic cation transporter efflux of metformin. The investigators hypothesize that the co-administration of metformin and nizatidine will reduce the renal clearance (CLR) of metformin leading to increased plasma concentrations and potential risk for toxicities. Knowledge of the pharmacokinetic interaction profile of metformin with organic transporter inhibitors, such as nizatidine, is important to help develop safer more effective drug therapy with reduced side effects.
详细描述
Screening Procedures:
Prior to enrollment, subjects will be asked to come to the Clinical and Translational Science (CTSI) Clinical Research Centre (CRC) at San Francisco General Hospital (SFGH). The study protocol and procedures will be explained in detail, all questions will be answered, and subjects will be provided a consent form to sign. The screening visit will be conducted within 14 days of the first inpatient visit i.e. first metformin alone or metformin with nizatidine dosing day.
Only after subjects have consented to participate in the study will the screening procedures commence. All subjects recruited in this study will have already consented to the pharmacogenomics in ethnically diverse populations (SOPHIE) study, a previously established cohort of healthy people living in San Francisco. A review of the subject's medical history and health questionnaire will be conducted to re-assess health status and confirm eligibility (see attached health questionnaire). Changes in medication or drug use history will be noted during the study.
During the screening visit, vital signs as well as blood and urine samples will be taken from all subjects for laboratory analysis. A single blood sample (10 mL) will be taken by venipuncture to measure a complete blood count (CBC), electrolytes, blood urea nitrogen (BUN), creatinine, and liver function tests (LFTs) to screen for anemia and renal or hepatic insufficiency (see Inclusion/Exclusion Criteria).
Procedures During Main Study:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 18-45 years
- •Male or female
- •If female, using appropriate contraception
- •Healthy as judged by medical examination, medical history and normal biochemical and hematological measures
- •Normal urinalysis and renal function
- •Understand the nature and purpose of the study and provide informed consent
排除标准
- •Pregnant or lactating woman (female subjects will have a urine pregnancy test at the screening visit)
- •Abnormal bone marrow function (leukocyte, neutrophil, or platelet counts outside the normal range)
- •History of hypersensitivity or allergic reaction to metformin or nizatidine
- •Risk of congestive heart failure requiring pharmacologic treatment (medical history)
- •History of renal or hepatic dysfunction (e.g., CLcr <60mL/min, ALT >80U/L, AST>60 U/L)
- •Anemic (hemoglobin <12 g/dL)
- •Use of any medications (including over the counter products, herbal products, or mineral supplements) with the exception of a daily vitamin or oral contraceptives. In particular use of medications that are known to interfere with the pharmacokinetics of metformin and nizatidine such as cimetidine, cetirizine, ketoconazole, procainamide, St. John's Wort, and testosterone are prohibited.
- •Laboratory parameters that are more than 2 standard deviations from the laboratory mean
- •Subject carries a MATE2K gene variant that is predicted to effect MATE2K protein expression
研究组 & 干预措施
Metformin
Subjects will be dosed with Metformin alone (850 mg)
干预措施: Metformin (Drug)
Metformin and Nizatidine
Subjects will be dosed with metformin in conjunction with nizatidine
干预措施: Metformin and nizatidine (Drug)
结局指标
主要结局
Composite of Pharmacokinetics of co-administration of nizatidine & metformin in healthy volunteers.
时间窗: 24 hours
Cmax and Tmax will be determined from AUC-time curve Glomerular filtration rate (GFR) will be approximated by measured creatinine clearance using the following equation:GFR calculation: GFR = CLcreatinine = (Urinary creatinine \* V) / (Plasma creatinine)
次要结局
未报告次要终点