Determining Equivalence Dose for Oral Versus Sublingual Administration of Tacrolimus in Hepatic Receptors

After liver transplantation one of the most important cost, for both patients and their health insurance system, is immunosuppressive drug therapy. Tacrolimus (FK 506) is considered the cornerstone of immunosuppressive therapy in solid organ transplantation. Oral administration is the usual route, however, sublingual (SL) administration has been recently reported. This method of administration avoids first pass metabolism and allows an alternative route after transplant surgery, particularly in those patients who should extend the period of fasting (prolonged intubation, ileus, etc). Interestingly, in some studies, the dose of tacrolimus SL required to maintain similar plasma concentrations compared with oral administration, is significantly lower, even up to 50%, which can result in considerable savings in short and long term. Among these studies, only one was conducted in liver recipients. This study suggest that SL administration of tacrolimus could allow to obtain similar concentrations compared with oral administration. The design of this study did not assess the existence of differences in the dose required and only included six patients.

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Key information

Conditions

Evidence of Liver Transplantation Effects of Immunosuppressant Therapy

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Pontificia Universidad Catolica de Chile

Santiago, 8330024, Chile

About this study

The patient will be scheduled fasting to liver transplant unit where the pharmacokinetic study was performed. After installation of the venous needle, blood samples will be collected on 4 ml tubes with EDTA as an anticoagulant at the following intervals of time in hours: 0 (immediately before the oral administration of tacrolimus); 0.5; 1.0; 1.5; 2; 4; 6; 9 and 12 h. post-dose. Once the blood samples taken, the tubes will be plugged, invest gently to mix with anticoagulant and stored at -20 ° C until analysis.

Subsequently, tacrolimus administration was change to sublingual route and dose was adjusted to obtain similar trough levels to those determined on per oral administration. The capsule be opened and its contents shall be deposited in the sublingual mucosa. To be ensure that drug will be absorted the patient will be instructed to insistently that after sublingual placement of the drug, should not swallow the capsule content for at least 15 minutes. The same pharmacokinetic study described for the oral route will be performed.

Breakfast will be administered 2 hours after ingesting the drug and lunch and dinner 6 and 10 hours after respectively. Fluid intake is discretionary.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Outline of immunosuppression that includes tacrolimus dosing every 12 hours.
Stable plasma levels of tacrolimus in 3 consecutive measurements.
Stable blood tests: biochemical profile, creatinine and liver profile.
Absence of treatment with drugs that have interaction with tacrolimus (antifungal and diltiazem) and use of grapefruit juice.
Absence of active bacterial or viral infection and rejection episodes within 8 weeks prior.

Exclusion criteria

Treatment and study plan

Tacrolimus

Drug

compared oral administration versus sublingual administration of tacrolimus.

Other names: FK506

Primary outcomes

Compare tacrolimus exposure using per oral and sublingual administration employing AUC (Area Under the Curve).

Time frame: 30 days

compared oral administration versus sublingual administration of tacrolimus

Secondary outcomes

Compare tacrolimus dose necessary to obtain similar trough levels employing per oral and sublingual administration

Time frame: 30 days

compared oral administration versus sublingual administration of tacrolimus

Sponsors and collaborators

Lead sponsor

Pontificia Universidad Catolica de Chile

Other

Registry information

Acronym: FKosl

Important dates

Study start: 2015
Primary completion: 2016
Study completion: 2016
First posted: Nov 20, 2015
Registry last updated: Oct 12, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed