Drug-Drug Interaction Study With Metformin and Nizatidine

• Status: Completed
• Trial end date: 2013-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of California, San Francisco
• Collaborator: National Institute of General Medical Sciences (NIGMS)
• Treatments: Metformin; Nizatidine

Criteria

Inclusion Criteria:

1. Age 18-45 years

2. Male or female

3. If female, using appropriate contraception

4. Healthy as judged by medical examination, medical history and normal biochemical and hematological measures

5. Normal urinalysis and renal function

6. Understand the nature and purpose of the study and provide informed consent

Exclusion Criteria:

1. Pregnant or lactating woman (female subjects will have a urine pregnancy test at the screening visit)

2. Abnormal bone marrow function (leukocyte, neutrophil, or platelet counts outside the normal range)

3. History of hypersensitivity or allergic reaction to metformin or nizatidine

4. Risk of congestive heart failure requiring pharmacologic treatment (medical history)

5. History of renal or hepatic dysfunction (e.g., CLcr <60mL/min, ALT >80U/L, AST>60 U/L)

6. Anemic (hemoglobin <12 g/dL)

7. 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.

8. Laboratory parameters that are more than 2 standard deviations from the laboratory mean

9. Subject carries a MATE2K gene variant that is predicted to effect MATE2K protein expression