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

NCT ID: NCT02608606

Last Updated: 2016-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2016-03-31

Brief Summary

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.

Detailed Description

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.

Conditions

Evidence of Liver Transplantation; Effects of Immunosuppressant Therapy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

oral administration of tacrolimus

Oral administration of tacrolimus (FK506) in the usal dose and measuring plasmatic levels at hours 0, 0.5, 1, 2, 3, 4 and 6. Measuring AUC.

Group Type: NO_INTERVENTION

No interventions assigned to this group

sublingual administration of tacrolimus

sublingual administration of tacrolimus (FK506) in the dose that allows similar plasmatic level at time 0 compared with the oral administration, and measuring plasmatic levels at hours 0, 0.5, 1 , 2, 3 , 4 and 6. Measuring AUC.

Group Type: ACTIVE_COMPARATOR

Tacrolimus

Intervention Type: DRUG

compared oral administration versus sublingual administration of tacrolimus.

Interventions

Tacrolimus

compared oral administration versus sublingual administration of tacrolimus.

Intervention Type: DRUG

Other Intervention Names

FK506

Eligibility Criteria

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

-

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pontificia Universidad Catolica de Chile

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carlos Benitez, Hepatologist

Role: PRINCIPAL_INVESTIGATOR

Pontificia Universidad Catolica de Chile

Locations

Pontificia Universidad Catolica de Chile

Santiago, , Chile

Countries

Chile

References

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Other Identifiers

FKoral-sl

Identifier Type: -

Identifier Source: org_study_id