Impact of Polymorphisms of OAT1, OAT3, and OCT2 on Transportation of Potential Nephrotoxic Drugs

NCT00251017 | Completed

• 2 other identifiers: 9361701301DOH94-td-d-113-035(2)
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Transporters in kidney are critical in detoxification and elimination of xenobiotics from systemic circulation, and thus are major determinants of drug response and sensitivity. Transporters in the renal epithelium control the exposure of renal cells to nephrotoxic drugs and environmental toxins and thus determine xenobiotic-induced nephrotoxicity. Organic anion transporters (OATs) and organic cation transporters (OCTs) are two major classes of secretory transporters in the mammalian kidney. Among the uptake transporters, OAT1, OAT3, or OCT2 appear to be particularly important in the renal basolateral membrane to transport a large variety of endogenous and therapeutic compounds. Recently, rapid advances in single nucleotide polymorphisms (SNPs) mapping can now be applied to characterize the individual patients who suffer adverse effects to a drug, or those for whom a drug shows efficacy. The aim of this study was to identify and functionally characterize OCT2 variants as a first step towards understanding whether genetic variation in OCT2 may contribute to interindividual differences in renal elimination of vancomycin. Taiwanese patients will be screened and 12 coding region variants of OCT2 will be identified. The non-synonymous variants of OAT1, OAT3, or OCT2 will then be constructed and characterized using in vitro human renal cell models. It is to establish whether genetic variants in OAT1, OAT3, or OCT2 are likely significant contributors to intersubject variability in drug response. In addition, approaches toward prevention of some drug-induced nephrotoxicity are discussed, based on molecular mechanisms of renal accumulation of these drugs. Perhaps the researchers' understanding of OAT1, OAT3, or OCT2 in pharmacogenomics may contribute to the goal of individualized drug therapy. Development of new strategies based on the understanding of their cellular handing may achieve safer and more effective therapy for personalized medicines.

Conditions

Adverse Effects

Keywords

single nucleotide polymorphisms (SNPs); personalized medicines; Subjects 16 years of age or older, of either sex.; Subjects have a medication including vancomycin

Outcome Measures

Primary Outcomes (1)

• Single nucleotide polymorphism (SNP), plasma creatinine and vancomycin concentration

  0, 2 hour after Vancomycin administration

Study Arms (1)

Vancomycin

ACTIVE COMPARATOR

Effects of OCT2 genetic variation in renal elimination of Vancomycin

Procedure: Vancomycin; Procedure: DNA are extracted from the whole blood of subjects

Interventions

Vancomycin PROCEDURE

Two hour creatinine clearance before and after vancomycin

Vancomycin

DNA are extracted from the whole blood of subjects PROCEDURE

Vancomycin

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects 16 years of age or older, of either sex.
• Subjects have a medication including vancomycin
• Subjects have realistic expectations of the benefit and limitation of the augmentation procedure, as determined by a willingness to sign the informed consent form after it has been carefully explained.

You may not qualify if:

• Subjects have a medical condition that increased the risks of study participation (including pregnancy and poor renal function)
• Subjects are taking medications (nephrotoxicants) that could confound study results.
• Subjects presenting with history of autoimmune disorder, septic shock, or multiple organ failure.
• Subjects with renal failure undergoing dialysis (hemodialysis \[HD\] or continuous ambulatory peritoneal dialysis \[CAPD\]), continuous venovenous hemofiltration (CVVH), or continuous arteriovenous hemodiafiltration (CAVHDF).

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• Department of Health, Executive Yuan, R.O.C. (Taiwan): collaborator

Study Sites (1)

Department of Surgery, National Taiwan University Hospital

Taipei, 100, Taiwan

Location

MeSH Terms

Interventions

Vancomycin

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Ji-Wang Chern, Ph.D.

  National Taiwan University

  STUDY CHAIR

• Wen-Je Ko, M.D, Ph.D

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

• Fe-Lin Lin, Ph.D.

  National of University

  PRINCIPAL INVESTIGATOR

• Chiung-Hua Huang, M.S

  National Taiwan University

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 8, 2005
• First Posted: November 9, 2005
• Study Start: July 1, 2005
• Primary Completion: June 1, 2006
• Study Completion: June 1, 2006
• Last Updated: December 27, 2012

Record last verified: 2012-12

Locations

TW (1)