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Pharmacokinetics of Sublingual Versus Oral Tacrolimus in Patients Awaiting Kidney Transplantation

Information source: Weill Medical College of Cornell University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Kidney Failure, Chronic

Intervention: Tacrolimus/Clotrimazole Troche (Drug); Tacrolimus/Nystatin Suspension (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Weill Medical College of Cornell University

Official(s) and/or principal investigator(s):
Meredith J Aull, Pharm.D., Principal Investigator, Affiliation: NewYork-Presbyterian Hospital


Tacrolimus (Prograf) belongs to a class of medications known as the calcineurin inhibitors. It is a maintenance drug that is used to prevent rejection in kidney, liver, and heart transplant recipients. Calcineurin inhibitors display high pharmacokinetic (the body's effects on a drug) variability and necessitate use of blood tests to ensure that adequate drug levels are present to maintain effectiveness and safety. The amount of oral tacrolimus that is absorbed varies in all patient populations studied. Tacrolimus is metabolized or broken down for elimination by the liver and small intestine via cytochrome P450 (CYP)3A4, CYP 3A5, and p-glycoprotein enzyme systems. Enzyme activity is affected by several single nucleotide polymorphisms (SNPs) in an individuals genetic make-up and differences in expression may contribute to variations in tacrolimus pharmacokinetics. There are number of drug-drug interactions where concomitantly administered medications can increase or decrease this break down of tacrolimus. Early after transplant or at times when tacrolimus cannot be taken by mouth, alternative routes of administration are sought. Although an intravenous (through the vein) product is available, it can be toxic to the kidneys and has been associated with allergic reactions. Studies in lung transplant recipients have utilized sublingual (under the tongue) tacrolimus administration with successful outcomes. Drug delivery via the oral mucosa is an alternative method of systemic drug administration which offers an alternative when oral administration is impractical (gastrointestinal dysmotility, reduced drug absorption, intestinal failure, difficulty in swallowing, or in those with nausea or vomiting). Administration of tacrolimus by the sublingual route allows for direct entry into the systemic circulation and bypasses problems associated with drug absorption and breakdown that take place in the small intestine. In order to learn more about the possible role of sublingual tacrolimus among transplant recipients we will administer tacrolimus sublingually. In addition, we will evaluate differences in expression and bioactivity of SNP polymorphisms and their effects in tacrolimus pharmacokinetics. Patients awaiting kidney transplantation who are listed on the kidney transplant waiting list or those with upcoming living donor transplants at our center will be administered five doses of sublingual tacrolimus followed by five doses of oral tacrolimus. We will evaluate and then compare the pharmacokinetic characteristics of sublingual and oral tacrolimus administration among the study participants. The purpose of this study is to assess the pharmacokinetic and pharmacodynamic parameters of tacrolimus after sublingual and oral administration. A secondary objective is to assess the drug-drug interaction between concomitant therapy with clotrimazole.

Clinical Details

Official title: Pharmacokinetic Evaluation of Sublingual Versus Oral Tacrolimus Administration in Patients Awaiting Kidney Transplantation

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Health Services Research

Primary outcome: Pharmacokinetic evaluation (absorption, distribution, elimination, area under the curve) between sublingual and oral administration routes.

Secondary outcome: Impact of drug interaction between tacrolimus and clotrimazole troche vs. nystatin suspension. Evaluate genotype polymorphisms that influence CYP3A4, CYP3A5, and p-glycoprotein expression to determine impact on sublingual and oral tacrolimus delivery.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria:

- Adult patients awaiting kidney transplantation aged ≥ 18 years

Exclusion Criteria:

- Patients concurrently treated with medications that interact with tacrolimus (other

than clotrimazole)

Locations and Contacts

NewYork-Presbyterian Hospital, New York, New York 10065, United States
Additional Information

Starting date: February 2008
Last updated: November 4, 2010

Page last updated: August 23, 2015

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