Related Experiment Video
Updated: Jan 1, 2026
09:34
An Automated Culture System for Use in Preclinical Testing of Host-Directed Therapies for Tuberculosis
Published on: August 16, 2021
2.2K
Determining therapeutic trough ranges for linezolid
1Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Summary
Therapeutic drug monitoring for linezolid (LZD) optimizes dosing. Achieving a trough concentration of 2-5 μg/mL is recommended for gram-positive infections with low MIC values to ensure effective treatment.
Area of Science:
- Pharmacology
- Infectious Diseases
- Clinical Pharmacy
Background:
- Linezolid (LZD) is a crucial oxazolidinone antibiotic for treating Gram-positive bacterial infections.
- Optimizing LZD dosage through therapeutic drug monitoring (TDM) is essential for maximizing efficacy and minimizing toxicity.
- The established therapeutic target for LZD is an area under the concentration-time curve over 24 hours to minimum inhibitory concentration (AUC/MIC) ratio greater than 100.
Purpose of the Study:
- To determine the optimal trough concentration ranges of linezolid (LZD) that achieve the therapeutic target of AUC/MIC > 100.
- To evaluate the correlation between LZD trough concentrations and the 24-hour AUC.
- To provide dosing guidance for LZD based on different minimum inhibitory concentration (MIC) values.
Main Methods:
- Simulation of concentration-time profiles for 999 virtual patients using a validated LZD pharmacokinetic model.
- Estimation of the 24-hour AUC for each virtual patient using the trapezoidal method.
- Determination of trough ranges associated with achieving an AUC/MIC ratio > 100 for MIC values of 1, 2, and 4 μg/mL.
Main Results:
- A strong correlation was observed between LZD trough concentrations and AUC (R² = 0.87).
- A trough concentration range of 2-5 μg/mL achieved an AUC₀-₂₄ > 100 in 99% of simulated patients with MIC ≤ 2 μg/mL.
- Higher trough concentrations (5-8 μg/mL) were needed for MIC = 2 μg/mL, and achieving the target AUC/MIC > 100 was challenging at an MIC of 4 μg/mL, increasing toxicity risk.
Conclusions:
- Trough concentration monitoring is a reliable method for optimizing linezolid (LZD) therapy.
- Recommended trough ranges are 2-5 μg/mL for MIC < 2 μg/mL and 5-8 μg/mL for MIC = 2 μg/mL to achieve therapeutic AUC/MIC targets.
- Treatment of infections with linezolid (LZD) at an MIC of 4 μg/mL requires careful consideration due to difficulties in reaching the therapeutic target without elevated toxicity risk.
Related Concept Videos
01:15Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations
191
Gentamicin, an aminoglycoside antibiotic, is commonly administered via intermittent intravenous infusion to treat severe infections. An intermittent one-hour infusion of gentamicin, administered at eight-hour intervals, allows for precise control of plasma drug concentrations, minimizing toxicity while ensuring therapeutic efficacy. Pharmacokinetic principles govern the dynamics of plasma concentrations and can be mathematically described using specific equations.The plasma drug concentration...
191
01:19Dosage Interval and Administration Route: Determination Methods
169
A medication’s effectiveness largely depends on its appropriate dosage and the route of administration. Dosage ensures that a sufficient drug concentration is maintained in the bloodstream to elicit the desired therapeutic effect without causing toxicity. The route of administration affects the drug's bioavailability, rate of absorption, and onset of action, which are crucial for achieving optimal therapeutic outcomes. Drug dosage calculations are critical to tailoring therapy to...
169
01:25Dosage Regimen: Multiple Oral Dosage
180
Understanding how a drug's concentration fluctuates within the body over time is crucial in pharmacokinetics, particularly with multiple oral doses. A graphical representation of multiple oral dosages provides insight into these dynamics. Typical accumulation curves of a drug's concentration in the body reveal a sawtooth pattern, indicating periodic peaks and troughs correlating with each dose administration and the drug's subsequent elimination.The plasma concentration at any time during an...
180
01:26Pharmacokinetics in Pediatric Patients: Drug Excretion
168
In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...
168
01:29Therapeutic Drug Monitoring: Affecting Factors
146
Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.
146
01:26Therapeutic Drug Monitoring: Drug Analysis Methods
137
Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood or body tissues to tailor drug therapy effectively. This monitoring is critical for managing drugs with narrow therapeutic indices like digoxin and phenytoin, ensuring they are both safe and effective. For instance, monitoring theophylline levels in asthma patients involves precision and sensitivity to adjust doses according to individual responses to therapy, ensuring efficacy and...
137