ArticleTransplantation proceedings2025
Intramuscular Tacrolimus Pharmacokinetics in a Pediatric Porcine Model for Partial Heart Transplantation.
Article in Transplantation proceedings, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveThe cornerstone of immunosuppression for transplantation is tacrolimus. One of the most reliable routes for administering tacrolimus in porcine models is intramuscular injection. However, the pharmacokinetics of intramuscular tacrolimus in piglets remain unexplored. Here, we close this gap in knowledge to guide intramuscular tacrolimus dosing in pediatric porcine transplant models.
methodIn the dosing trial, piglets (n = 7) underwent partial heart transplantation. Post-operatively, the piglets received immunosuppression with tacrolimus at daily doses between 0.07-0.4mg/kg. In the pharmacokinetic study, piglets (n = 6) underwent external jugular line placement. After a baseline blood draw, 0.25mg/kg of intramuscular tacrolimus was administered, and serial blood draws were performed to determine tacrolimus blood levels. The data was statistically analyzed to determine the pharmacokinetic parameters.
resultsThe dosing trial showed that intramuscular tacrolimus daily doses between 0.217-0.421mg/kg most consistently achieved tacrolimus blood levels within the therapeutic window. Therefore, 0.25mg/kg was used for the pharmacokinetic study. This revealed a half-life of 7.7 ± 0.9 hours, an average elimination constant of 0.09 ± 0.01, and an average volume of distribution of 30.9 ± 5.3 liters.
conclusionsIntramuscular tacrolimus achieves reliable blood levels with a predictable half-life. Despite high peak blood concentrations, a daily dose of 0.25 mg/kg did not result in clinical or laboratory evidence of toxicity.
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