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Levornidazole Tablets: A Comprehensive Pharmacokinetic Study

Introduction

Levornidazole is an innovative nitroimidazole antimicrobial agent known for its efficacy against anaerobes. This article explores the pharmacokinetic (PK) profile of levornidazole tablets and proposes an optimal dosing regimen based on pharmacokinetic/pharmacodynamic (PK/PD) analysis. The study focuses on the effects of single and multiple oral doses of levornidazole tablets in healthy Chinese subjects.

Methods

A single-center, randomized, double-blind, placebo-controlled study was conducted to evaluate the PK parameters of levornidazole tablets. The study included a single ascending dose (250, 500, 1000, and 1500 mg) and multiple doses of 500 mg levornidazole q12h for seven days. The impact of food on PK and absolute bioavailability was also examined at the 500 mg dose level. Blood and urine samples were collected to determine the PK parameters.

Pharmacokinetic Profile

Absorption

Following administration of single doses (ranging from 250 to 1500 mg), levornidazole tablets exhibited rapid and complete absorption. Plasma concentration peaked approximately 0.5 hours after ingestion. The maximal concentration (Cmax) and exposure (AUC0-∞) of levornidazole increased proportionally with the dose administered.

Food Effect and Bioavailability

The study revealed that the absorption extent of levornidazole tablets was not affected by a high-fat diet. The absolute oral bioavailability of levornidazole tablets was estimated to be 98.3% ± 7.6%. This high bioavailability can be attributed to the large apparent volume of distribution (48.68 ± 4.92 liters) and long half-life (11.93 ± 1.28 hours) observed in healthy Chinese subjects.

Urinary Excretion

Levornidazole exhibited low urinary excretion, with only 7.99% of the administered dose excreted in the urine.

Pharmacokinetic/Pharmacodynamic Analysis

To assess the efficacy of levornidazole tablets, a pharmacokinetic/pharmacodynamic (PK/PD) analysis was performed. Monte Carlo simulation was used to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR). The results indicated that levornidazole tablets administered at either 500 mg q12h or 750 mg q24h achieved a CFR > 95.4% and PTA > 99% for B. fragilis infections with a minimum inhibitory concentration (MIC) ≤ 1.0 mg/l.

Proposed Dosing Regimen

Based on the PK/PD analysis, a dosing regimen of levornidazole tablets was proposed for B. fragilis infections. The recommended dosages are as follows:

  • Levornidazole tablets 500 mg q12h

  • Levornidazole tablets 750 mg q24h

These dosages are expected to achieve the desired efficacy in treating B. fragilis infections.

Conclusion

The pharmacokinetic study of levornidazole tablets in healthy Chinese subjects revealed that these tablets are rapidly and completely absorbed, with extensive distribution and a long half-life. The study also demonstrated the high bioavailability of levornidazole tablets and their low urinary excretion. The proposed dosing regimen of levornidazole tablets is expected to effectively treat B. fragilis infections.



Disclaimer: This article is for informational purposes only and does not constitute medical advice. Consult a healthcare professional for proper diagnosis and treatment.

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