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Pharmacokinetic Evaluation of Sublingual Versus Oral Tacrolimus Administration in Patients Awaiting Kidney Transplantation
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.
Details
| Lead sponsor | Weill Medical College of Cornell University |
|---|---|
| Phase | Phase 4 |
| Status | COMPLETED |
| Enrolment | 5 |
| Start date | 2008-02 |
| Completion | 2009-12 |
Conditions
- Kidney Failure, Chronic
Interventions
- Tacrolimus (Arm B)
- Clotrimazole Troche
- Tacrolimus (Arm A)
- Nystatin Suspension
Primary outcomes
- C0 (ng/mL) — Day 3 and Day 8, time 0 (before tacrolimus dose)
Trough concentration - Cmax — Day 3 and Day 8, at time of maximum concentration
Maximum concentration (ng/mL) - Tmax — Day 3 and Day 8, time of maximum concentration
Time to Maximum concentration (hours) - Estimated AUC 0-6 — Day 3 and Day 8, calculated based on concentrations measured between hours 0 and 6
Area Under the Concentration-Time Curve from 0-6 hours (mg-hr/L) - Tacrolimus Powder Dissolution Time — Day 3, minutes to powder dissolution
Tacrolimus Powder Dissolution Time during Sublingual Administration (minutes)
Countries
United States