Evaluation of Renal Drug Transport in Healthy Volunteers

NCT00690014 | Completed DMC

• 2 other identifiers: H-261291R15GM072526-01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The process of drug elimination that occurs within the kidneys is complex, and involves filtration, secretion and absorptive mechanisms. Many drugs, metabolites and toxins, including organic anions and cations, rely on renal mechanisms for elimination from the body. Failure to recognize the contribution of renal mechanisms involved in drug elimination during the drug development process can result in drug interactions or toxicity in clinical trials. This is increasingly important due to the use of OAT1 inhibitors such as probenecid that are being used in adjuvant treatment regimens. Thus, in order to more fully understand the effects renal disease, drugs and nephrotoxins on the renal transport pathways of tubular secretion in humans, novel approaches that incorporate both in vitro (experimental) as well as clinical observations (clinical trial), also called in-vitro/in-vivo correlations (IVIVC) need to be developed. These methods can then be used to identify and evaluate specific kidney "probe" drugs that undergo extensive tubular secretion. Such approaches are needed to characterize drug clearance by tubular mechanisms and to identify potentially significant drug-drug interactions prior to exposure to patients in Phase 2 and 3 clinical trials. This investigator-initiated pilot project aims to determine the pharmacokinetics of selected FDA-approved compounds (PAH, iothalamate) for use in IVIVC model development. The proposed research is innovative, because it involves a translational approach to development of an IVIVC model applied to renal drug clearance. It is our expectation that the resultant approach will further our understanding of pharmacogenomics, inter-subject variability and renal drug clearance. This approach will generate important new information regarding in vitro drug-drug interactions in light of many new and potent OAT1 blocking agents being introduced for the treatment of human diseases. In future studies, we hope to fully characterize the effects of diseases such as diabetes, hypertension, and nephropathy on renal drug transport mechanisms using IVIVC models. We expect that results from this NIH-funded study will provide needed preliminary data to design future pharmacogenomic and drug interaction studies in humans.

Conditions

Kidney Disease

Keywords

OAT; GFR; renal function; PAH

Outcome Measures

Primary Outcomes (1)

• Effect of probenecid on renal clearance of PAH (renal function probe)

  24 hours

Study Arms (1)

A

EXPERIMENTAL

Drug: probenecid

Interventions

probenecid DRUG

500 mg q 6 hrs

A

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adult, aged 18 to 40 years
• Healthy based on review of past medical history and physical examination (normal biochemical screen and urinalysis)
• Signed inform consent

You may not qualify if:

• Any medications taken within 48 hours prior to study
• History of gout or gouty arthritis
• History of uric acid
• Kidney stones
• History of known allergic or adverse reactions to diagnostic iodine containing compounds including iothalamate, PAH or probenecid, will be excluded.
• Subjects with current or preexisting liver disease (including hepatitis) as evidenced by elevated INR, liver transaminases (AST/ALT), bilirubin, or serum albumin \< 3.0 g/dL.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Institutes of Health (NIH): collaborator
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

University of Maryland GCRC

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Kidney Diseases

Interventions

Probenecid

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Study Officials

• Thomas Dowling, PhD

  University of Maryland, College Park

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2008
• First Posted: June 4, 2008
• Study Start: August 1, 2006
• Primary Completion: April 1, 2007
• Study Completion: June 1, 2007
• Last Updated: May 11, 2021

Record last verified: 2021-05

Locations

US (1)