Sublingual administration improves systemic exposure of tacrolimus in kidney transplant recipients: comparison with oral administration

Federico, Stefano; Carrano, Rosa; Sabbatini, Massimo; Nappi, Riccardo; Russo, Luigi; Apicella, Luca; Balletta, M; Santangelo, Michele; Mosca, Teresa; Tarantino, Giovanni; Capone, Domênico

doi:10.1111/eci.12644

Cited by 8 publications

(13 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Decreased dose requirements were described in some clinical studies after sublingual administration of tacrolimus compared to the oral route 21,24 . Through simulations, our model predicts the same pattern, as we observed an approximately 10–20% higher AUC 0–12h in the sedated than in the nonsedated status between 7 and 21 days post transplantation.…”

Section: Discussionsupporting

confidence: 70%

“…Sublingual absorption involves dissolution in a small volume of saliva, drug diffusion through the lipophilic cell membranes and direct passage through the oral epithelium to the systemic circulation, 19,20 bypassing the first‐pass effect. These processes may explain the 50–75% decreased dose requirements previously reported in adult patients receiving tacrolimus sublingually who were trained not to swallow the dose 16,21–24 . Reports of sublingual tacrolimus administration, dosing, PK and safety are scarce and mainly available in adults with thoracic transplantation or healthy volunteers as part of studies for mechanistic purposes 18,23 .…”

Section: Introductionmentioning

confidence: 99%

“…These processes may explain the 50-75% decreased dose requirements previously reported in adult patients receiving tacrolimus sublingually who were trained not to swallow the dose. 16,[21][22][23][24] Reports of sublingual tacrolimus administration, dosing, PK and safety are scarce and mainly available in adults with thoracic transplantation or healthy volunteers as part of studies for mechanistic purposes. 18,23 Therefore, comprehensive characterization of the absorption…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Population pharmacokinetics of sublingually administered tacrolimus in infants and young children with liver transplantation

Riva

Ibarra

Parra-Guillén

et al. 2022

Brit J Clinical Pharma

View full text Add to dashboard Cite

Aims: Pharmacokinetics of tacrolimus after sublingual administration is not characterized in paediatric liver transplant patients. Therefore, we aimed to develop a population pharmacokinetic model of sublingually administered tacrolimus in patients who cannot swallow the capsules due to their age, sedation status and/or mechanical ventilation during the first weeks post-transplantation. Methods: Demographic, clinical and pharmacological variables, including tacrolimus whole blood concentrations obtained from therapeutic drug monitoring and data from dense-sampling pharmacokinetic profiles, were recorded in 26 paediatric patients with biliary atresia who underwent liver transplantation between 2016 and 2021. Population pharmacokinetic analysis was performed with NONMEM v7.4. Results: Disposition of tacrolimus was best characterized by a 2-compartment model with clearance achieving half of the maximum elimination capacity (CL MAX = 4.1 L/h) at 4.6 days post-transplantation (T 50 ). Compared to sedated patients, nonsedated status showed an increased first-order absorption rate constant (1.1 vs. 0.1 h À1 ) and a 24% reduction in bioavailability (F NS ) at 14 days post-transplant. The model was ableThe authors confirm that the Principal Investigator for this paper is Daniel Buamscha, MD, and that he had direct clinical responsibility for patients.

show abstract

Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Population pharmacokinetics of sublingually administered tacrolimus in infants and young children with liver transplantation

Riva

Ibarra

Parra-Guillén

et al. 2022

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…This saved costs and offered an attractive option to intravenous and oral administration. 13 Concomitant use of drugs, which induce or inhibit CYP3A enzymes, alters the drug clearance and mandates more vigilant therapeutic drug monitoring and dose adjustment. 14 Changes in the motility of the gut affects absorption and overall drug exposure.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Untitled

Shrestha

2017

Exp Clin Transplant

View full text Add to dashboard Cite

Tacrolimus, a calcineurin inhibitor, has been the cornerstone of immunosuppressive regimens in renal transplant over 2 decades. This has significantly improved the outcomes of renal transplant, including reduction of acute rejection episodes, improvement of renal function and graft survival, and reduction of some of the adverse effects associated with cy closporine. However, use of tacrolimus is associated with a number of undesirable effects, such as nephrotoxicity, posttransplant diabetes mellitus, neurotoxicity, and cosmetic and electrolyte disturbances. To alleviate these effects, several strategies have been adopted to minimize or eliminate tacrolimus from maintenance regimens of immuno suppression, with some success. This review focuses on advancements in the under standing of the basic science related to tacrolimus and the clinical evidences that have examined the efficacy and safety of tacrolimus in renal transplant over the past 2 decades and highlights the future directions.

show abstract

“…By opening a capsule and placing the powder contents under the tongue, patients are able to achieve goal trough levels with minimal, if any, adverse effects. [7][8][9][10] In most published studies, the SL route shows excellent bioavailability due to direct absorption into the bloodstream through the oral mucosa. The area under the blood-concentration-time curve (AUC) was well correlated with whole blood trough levels, the current standard of care for therapeutic drug monitoring that guides dose adjustments to maintain concentrations within the desired therapeutic window.…”

Section: Introductionmentioning

confidence: 99%

Use of sublingual tacrolimus in adults undergoing hematopoietic cell transplant: A pilot study

May

Bartoo

Wolf

et al. 2021

J Oncol Pharm Pract

View full text Add to dashboard Cite

Introduction Orally administered tacrolimus is widely used in hematopoietic cell transplant patients, but multiple clinical situations may arise rendering oral administration infeasible. The undesirable sequelae of intravenous administration, including toxicity, challenges with administration and cost call for innovative solutions to conserve existing supply and optimize safety and efficacy of medication delivery. We sought to demonstrate feasibility of sublingual tacrolimus use and estimate a sublingual-to-oral (SL:PO) conversion ratio in the hematopoietic cell transplant setting. Methods Ten adults undergoing allogeneic hematopoietic cell transplant received tacrolimus 0.04 mg/kg/dose twice daily. Initial doses were given via sublingual route and a steady state trough level was collected after 4 consecutive doses. Participants were then switched to oral tacrolimus, the dose adjusted for a goal trough 8-12ng/mL, and another steady state trough was drawn. Total daily dose was divided by trough concentration for each route to determine the dosing ratio of SL:PO. Results Median trough level following sublingual administration was 11.3 ng/mL. Three of these were within goal, 3 were low (4.7–6.4 ng/mL) and 4 were elevated (15.9–18.6 ng/mL). Median SL:PO ratio was 1.02. In 5 participants the SL:PO ratio was <1 (range 0.57–0.94) and in 5 the ratio was ≥1 (range 1.10–1.92). No significant barriers or intolerance to sublingual tacrolimus use were noted. Conclusions Results demonstrate reliable absorption with sublingual tacrolimus use in patients undergoing hematopoietic cell transplant. Sublingual administration may allow for avoidance of the undesirable complications of IV tacrolimus, such as increased toxicities, required hospitalization for continuous infusion, risk of dose conversion and dilution errors and increased cost. Trial Registry name: Use of Sublingual Tacrolimus in Adult Blood and Marrow Transplant Patients, NCT04041219 https://clinicaltrials.gov/ct2/show/NCT04041219?term=NCT04041219&draw=2&rank=1

show abstract

Sublingual administration improves systemic exposure of tacrolimus in kidney transplant recipients: comparison with oral administration

Abstract: When oral administration of TCR is not advised, SL delivery represents an attractive option to IV administration.

Cited by 8 publications

References 29 publications

Population pharmacokinetics of sublingually administered tacrolimus in infants and young children with liver transplantation

Population pharmacokinetics of sublingually administered tacrolimus in infants and young children with liver transplantation

Untitled

Use of sublingual tacrolimus in adults undergoing hematopoietic cell transplant: A pilot study

Contact Info

Product

Resources

About