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Published on: August 30, 2018
Teicoplanin 24-h loading dose regimen using a decision tree model to target serum trough concentration of
Shoji Kondo1, Kazutaka Oda2, Tetsuya Kaneko3
1Department of Pharmacy, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto, Japan; Department of Infection Control, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto, Japan; Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences Kumamoto University, 5-1, Oe, Chuo-ku, Kumamoto, Japan.
Introduction:
Teicoplanin (TEIC) is typically administered as a loading dose over 36-48 h. Achieving an effective concentration quickly is expected to treat severe infections, such as sepsis and methicillin-resistant Staphylococcus aureus infections. We aimed to identify the TEIC loading dose to be completed within 24 h, targeting the concentration of 15-30 μg/mL and factors affecting the loading dose by utilizing the decision tree (DT) model.
Methods:
Patients treated with TEIC between January 2017 and December 2022 who met the 24-h loading dose regimen were enrolled. A LD22.5 (corrected TEIC loading dose targeting concentration of 22.5 μg/mL) was determined, factors affecting the concentration were extracted, and a DT model was constructed. The validity of the DT was assessed using the coefficient of determination (R2) in the DT and population pharmacokinetics (PopPK) models for LD22.5.
Result:
A total of 149 patients were divided into training (n = 104, 70 %) and test groups (n = 45, 30 %). We indicated an average of 14.5 mg/kg for LD22.5 and extracted four factors (estimated glomerular filtration rate, age, albumin, and C-reactive protein) from the DT model. The R2 values were 0.724, 0.695, 0.681, and 0.653 for the DT models (training and test groups) and two PopPK models, respectively.
Conclusion:
We established a 24-h loading dose regimen targeting the TEIC concentration of 15-30 μg/mL and identified four factors affecting the loading dose by using DT. By following the indicated DT algorithm flowchat, optimal decisions regarding the loading dose could be made for TEIC therapy.
Insights
This study developed a 24-hour teicoplanin (TEIC) loading dose regimen to quickly achieve therapeutic concentrations for severe infections. A decision tree model identified key patient factors influencing the optimal TEIC dose.
Area of Science:
- Pharmacology
- Infectious Diseases
- Clinical Pharmacy
Background:
- Teicoplanin (TEIC) is typically administered over 36-48 hours for severe infections.
- Rapid achievement of therapeutic TEIC concentrations (15-30 μg/mL) is crucial for treating serious conditions like sepsis and MRSA infections.
Purpose of the Study:
- To establish a teicoplanin loading dose regimen completed within 24 hours.
- To identify patient-specific factors influencing the optimal loading dose using a decision tree (DT) model.
Main Methods:
- A retrospective analysis of 149 patients receiving TEIC between January 2017 and December 2022.
- Development and validation of a DT model to determine a corrected TEIC loading dose (LD22.5) targeting 22.5 μg/mL.
- Assessment of DT model validity using R² values compared to population pharmacokinetic (PopPK) models.
Main Results:
- An average LD22.5 of 14.5 mg/kg was indicated.
- Four key factors influencing TEIC loading dose were identified: estimated glomerular filtration rate, age, albumin, and C-reactive protein.
- DT models achieved R² values of 0.724 (training) and 0.695 (test), comparable to PopPK models.
Conclusions:
- A 24-hour loading dose regimen for teicoplanin was successfully established.
- The study identified critical factors influencing TEIC dosing, enabling personalized treatment strategies.
- The developed DT algorithm provides a practical tool for optimizing teicoplanin loading doses.
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