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