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The Relationship Between Weight Indices and Blood Levels of Immunosuppressive Drugs in Renal Transplant Recipients
Shirinsadat Badri1,2, Bozorgmehr Dadkhah-Tehrani3, Abdolamir Atapour2
1Department of Clinical Pharmacy and Pharmacy Practice, Isfahan University of Medical Sciences, Isfahan, Iran.
Background:
Calcineurin inhibitors and mammalian target of rapamycin (mTOR) inhibitors are essential for maintaining transplanted organs. However, determining the appropriate dosage and predicting blood concentrations of these drugs based solely on net body weight may be inadequate. Previous studies have presented contradictory results regarding the impact of obesity on drug concentrations and transplant success.
Objectives:
This study aims to evaluate various weight indices to identify the most reliable indicator of weight that correlates with the blood levels of drugs used in organ transplantation.
Methods:
This retrospective descriptive study included patients from nephrology clinics affiliated with Isfahan University of Medical Sciences who were taking calcineurin and/or mTOR inhibitor drugs. Data extracted from medical records included demographic and clinical information, such as height, weight, and various weight indices (total/ideal/adjusted body weight, lean body mass (LBM), Body Mass Index, and predicted normal weight), as well as blood levels of immunosuppressive drugs at each patient's visit. The dosages of each drug (mg/kg) were analyzed to determine which weight indices best correlated with the obtained blood concentrations, using the Generalized Estimating Equation (GEE) model with logistic regression, an independent correlation matrix, and a binary distribution for data analysis.
Results:
The study analyzed the medical records of 71 patients. Trough (C0) concentrations of drugs were evaluated in relation to each weight index, and odds ratios (OR) were calculated for statistical comparison. All weight indices increased the likelihood of achieving appropriate concentrations for cyclosporine, tacrolimus, and sirolimus. Drug dosing based on LBM (OR: 1.028), ideal body weight (OR: 1.075), and total body weight (OR: 1.041) showed the strongest correlations with achieving proper blood levels for cyclosporine, tacrolimus, and sirolimus, respectively.
Conclusions:
Integrating various weight indices for calculating individualized doses (mg/kg) of each immunosuppressive drug increases the likelihood of achieving appropriate blood concentrations. However, the optimal weight index varies for each drug. Further studies, particularly those incorporating therapeutic drug monitoring (TDM) plans in transplant centers, are warranted to validate and generalize these findings, providing a potential avenue for improving immunosuppressive therapy and enhancing transplant outcomes.
Insights
Determining optimal immunosuppressive drug dosing for organ transplant patients requires individualized weight indices beyond simple body weight. Lean body mass, ideal body weight, and total body weight show strong correlations with achieving therapeutic drug levels.
Area of Science:
- Pharmacology and Transplant Medicine
- Clinical Pharmacy
- Immunosuppression Therapy
Background:
- Calcineurin and mTOR inhibitors are vital for transplant success.
- Standard dosing based on body weight may be insufficient.
- Obesity's impact on drug levels and transplant outcomes is debated.
Purpose of the Study:
- To identify the most reliable weight index for correlating with immunosuppressive drug blood levels in transplant patients.
- To evaluate various weight indices for optimizing drug dosage calculations.
Main Methods:
- Retrospective analysis of 71 transplant patients on calcineurin and/or mTOR inhibitors.
- Data included weight indices (total, ideal, adjusted body weight, LBM, BMI) and drug blood levels.
- Generalized Estimating Equation (GEE) model used to assess correlations.
Main Results:
- All evaluated weight indices improved the likelihood of achieving target drug concentrations.
- Lean body mass (LBM), ideal body weight, and total body weight demonstrated the strongest correlations for specific drugs.
- Odds ratios indicated significant associations between weight indices and therapeutic drug levels.
Conclusions:
- Individualized dosing using various weight indices enhances the probability of achieving target immunosuppressive drug concentrations.
- The optimal weight index for dosing varies among different immunosuppressive drugs.
- Further research with therapeutic drug monitoring is recommended to validate these findings and improve transplant outcomes.
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