Inter- and Intra-individual Variations in Metformin Pharmacokinetics - The Importance of Genes and Drug Interactions
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 228
- 试验地点
- 1
- 主要终点
- Metformin AUC
研究概览
简要总结
The investigators aim to investigate the interindividual variation in metformin AUC in a large cohort of healthy volunteers after a single dose of metformin. Part 1 is driven by the hypothesis that metformin AUC and renal clearance exhibit significant interindividual variation. However this has never been documented in a large cohort of healthy volunteers.
The investigators aim to investigate the potential interaction between codeine and metformin in the intestine. The hypothesis underlying part 3 is that the increased risk of early discontinuation of metformin during co-administration with codeine is primarily due to local inhibition of OCT1 via codeine at the intestinal level.
详细描述
Part 1: The investigators intend to investigate the inter-individual variation in metformin Area Under Plasma Concentration Curve (AUC) following a single dose of oral metformin based on the plasma concentration of metformin after 3 and 10 hours and urine collection for 24 hours . Part 2: The investigators intend to contribute with DNA and metformin AUC determinations from subjects from part 1 to a major international study that aime to highlight the Genome Wide Association (GWA) between the entire genome and variations in metformin pharmacokinetics (AUC) in a large group of healthy subjects and patients. Part 3: The investigators aim to investigate the potential interaction between codeine and metformin in the intestine.
The investigators secondary objective in part 3 is to investigate if the plasma concentration of morphine increases when codeine and metformin are given together due to competitive inhibition of the Organic cation transporter 1 (OCT1) transport protein (in the liver). Furthermore, the investigators will measure lactate after metformin ingestion as a proxy for metformin's effect on the intestinal mucosa, both after oral and intravenous metformin
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 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
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Oral Metformin
Oral metformin 1000mg will be given as a single dosis
干预措施: Oral metformin (Drug)
Intravenous metformin
Intravenous metformin 500mg will be injected as a single dosis
干预措施: Intravenous metformin (Drug)
Oral codeine and oral metformin
Codeine 25 mg will be given at 5 occasions with approximately 6 hours between each dosing. The fifth and last dose will be given together with 1000 mg oral metformin
干预措施: Oral codeine and oral metformin (Drug)
Oral codeine and intravenous metformin
Codeine 25 mg will be given at 5 occasions with approximately 6 hours between each dosing. The fifth and last dose will be given together with 500 mg metformin administrated as an injection.
干预措施: Oral codeine and intravenous metformin (Drug)
结局指标
主要结局
Metformin AUC
时间窗: Blood samples will be drawn in each of the 4 arms from ingestion of the drug/drugs and for 24 hours at suitable times. Urine is collected after ingestion of metformin for 24 hours.
Outcome of part 3; differences in AUC for metformin when given alone and together with codeine
次要结局
- Codeine AUC(Blood samples are collected for 6 hours after ingestion of the first codeine pill. Blood samples are also collected and measured for codeine, morphing, M3G,M6G for 6 hours after both oral and intravenous metformin)
- Lactate AUC(Blood samples for lactate will be drawn in each arm after metformin ingestion for 24 hours at suitable times)
研究者
Ida Kuhlmann
Principal investigator
University of Southern Denmark