Pharmacokinetics of Sublingual Versus Oral Tacrolimus in Patients Awaiting Kidney Transplantation
Condition: Kidney Failure, Chronic
MeSH terms: Renal Insufficiency; Kidney Failure, Chronic
Intervention: Tacrolimus (Arm B); Clotrimazole Troche; Tacrolimus (Arm A); Nystatin Suspension
Intervention description: Study day 1 (9a): Initiate sublingual (SL) tacrolimus and clotrimazole troche x 5 doses; Study day 3 (9a): Collection of pharmacokinetic parameters around the 5th SL tacrolimus dose; Study day 3 (9p): Start washout period, no drug administration (tacrolimus, clotrimazole); Study day 5 (9p): End washout period; Study day 6 (9a): Initiate oral tacrolimus and clotrimazole troche x 5 doses; Study day 8 (9a): Collection of pharmacokinetic parameters around the 5th oral tacrolimus dose; Study day 15: Contact subject by telephone to assess for any adverse effects. To ensure that dietary intake does not affect the absorption profile of tacrolimus we will ensure that breakfast is given 15 minutes prior to drug administration on the days of pharmacokinetic assessment (study day 3 and 8).; Study day 1 (9a): Initiate sublingual (SL) tacrolimus and clotrimazole troche x 5 doses; Study day 3 (9a): Collection of pharmacokinetic parameters around the 5th SL tacrolimus dose; Study day 3 (9p): Start washout period, no drug administration (tacrolimus, clotrimazole); Study day 5 (9p): End washout period; Study day 6 (9a): Initiate oral tacrolimus and clotrimazole troche x 5 doses; Study day 8 (9a): Collection of pharmacokinetic parameters around the 5th oral tacrolimus dose; Study day 15: Contact subject by telephone to assess for any adverse effects. To ensure that dietary intake does not affect the absorption profile of tacrolimus we will ensure that breakfast is given 15 minutes prior to drug administration on the days of pharmacokinetic assessment (study day 3 and 8).; Study day 1 (9a): Initiate sublingual (SL) tacrolimus and nystatin suspension x 5 doses; Study day 3 (9a): Collection of pharmacokinetic parameters around the 5th SL tacrolimus dose; Study day 3 (9p): Start washout period, no drug administration (tacrolimus, nystatin); Study day 5 (9p): End washout period; Study day 6 (9a): Initiate oral tacrolimus and nystatin suspension x 5 doses; Study day 8 (9a): Collection of pharmacokinetic parameters around the 5th oral tacrolimus dose; Study day 15: Contact subjects by telephone to assess for any adverse effects. To ensure that dietary intake does not affect the absorption profile of tacrolimus we will ensure that breakfast is given 15 minutes prior to drug administration on the days of pharmacokinetic assessment (study day 3 and 8).; Study day 1 (9a): Initiate sublingual (SL) tacrolimus and nystatin suspension x 5 doses; Study day 3 (9a): Collection of pharmacokinetic parameters around the 5th SL tacrolimus dose; Study day 3 (9p): Start washout period, no drug administration (tacrolimus, nystatin); Study day 5 (9p): End washout period; Study day 6 (9a): Initiate oral tacrolimus and nystatin suspension x 5 doses; Study day 8 (9a): Collection of pharmacokinetic parameters around the 5th oral tacrolimus dose; Study day 15: Contact subjects by telephone to assess for any adverse effects. To ensure that dietary intake does not affect the absorption profile of tacrolimus we will ensure that breakfast is given 15 minutes prior to drug administration on the days of pharmacokinetic assessment (study day 3 and 8).
Intervention MeSH terms: Clotrimazole; Miconazole; Nystatin; Tacrolimus
Phase: Phase 4
Study type: Interventional
Primary purpose: Health Services Research
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Kidney Transplantation; Tacrolimus (Prograf); Pharmacokinetics; Sublingual administration; Drug interactions (Cytochrome P450 and p-glycoprotein)

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. 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. 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 may allow for direct entry
      into the systemic circulation and bypasses problems associated with drug absorption and
      breakdown that take place in the small intestine.
    

Eligibility 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)