ArticleDrug design, development and therapy2024
Dosing Regimen Recommendations for Sirolimus in Adult Liver Transplant Recipients: Insights from a Population Pharmacokinetic Model.
Article in Drug design, development and therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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1 citing paper in PubMed.
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5 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Background: Sirolimus is a commonly used immunosuppressant administered after solid organ transplantation. It is characterized by a narrow therapeutic window and highly variable exposure, necessitating the identification of the sources of variability and design of individualized drug therapies. Aim: This study aimed to perform a population pharmacokinetic (PK) analysis of sirolimus in adult liver transplant recipients and develop dosing regimen recommendations according to patient characteristics. Methodology: A total of 216 measurements of whole blood sirolimus concentrations in 103 adult patients were obtained for analysis. Covariates influencing the PKs of sirolimus were investigated using a stepwise procedure. Monte Carlo simulations were conducted to recommend dosing regimens for patients with different levels of covariates. Results: A one-compartment model with first-order elimination provided the best fit of the data. Hematocrit (HCT) significantly influenced the apparent clearance of sirolimus. Monte Carlo simulations showed that for patients with a low HCT level of 28%, dosing regimens of 1.5 mg qd or 1 mg qd alternating with 1.5 mg qd should be recommended. For patients with a normal HCT level, the recommended dosing regimens were 1 mg qd, 2 mg qod, or 0.5 mg qd alternating with 1 mg qd. Conclusion: Based on our population PK model of sirolimus in adult liver transplant recipients, which has the largest sample size to date, we recommend to tailor dosing regimens to various HCT levels in such patients.
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