Population pharmacokinetic modeling of levodropropizine: extended application to comparative analysis between commercial formulations and exploration of pharmacokinetic effects of diet

Jeong, Seung-Hyun; Jang, Ji-Hun; Lee, Yong-Bok

doi:10.1007/s00210-023-02889-5

Cited by 1 publication

(2 citation statements)

References 24 publications

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“…As a result, existing reports [ 8 , 11 , 12 , 13 , 14 ] on levodropropizine have limited utility in exploring individualized clinical treatment factors and/or dose adjustments. Recently, a population pharmacokinetic study on levodropropizine was reported, focusing on differences in formulation and dietary factors [ 15 ]. However, in the previous study [ 15 ], the exploration of covariates linked to aspects of treatment effect related to clinical indications (such as eosinophilic asthma) in interpreting the pharmacokinetic diversity of levodropropizine was not performed.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, a population pharmacokinetic study on levodropropizine was reported, focusing on differences in formulation and dietary factors [ 15 ]. However, in the previous study [ 15 ], the exploration of covariates linked to aspects of treatment effect related to clinical indications (such as eosinophilic asthma) in interpreting the pharmacokinetic diversity of levodropropizine was not performed. This suggested the need for further expanded covariate explorations that closely link levodropropizine pharmacokinetic variability interpretations with clinical-indication-related factors.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic Analysis of Levodropropizine and Its Potential Therapeutic Advantages Considering Eosinophil Levels and Clinical Indications

Jang,

Cho,

Jeong

2024

Pharmaceuticals

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Levodropropizine is a non-narcotic, non-centrally acting antitussive that inhibits the cough reflex triggered by neuropeptides. Despite the active clinical application of levodropropizine, the exploration of its inter-individual pharmacokinetic diversity and of factors that can interpret it is lacking. The purpose of this study was to explore effective covariates associated with variation in the pharmacokinetics of levodropropizine within the population and to perform an interpretation of covariate correlations from a therapeutic perspective. The results of a levodropropizine clinical trial conducted on 40 healthy Korean men were used in this pharmacokinetic analysis, and the calculated pharmacokinetic and physiochemical parameters were screened for effective correlations between factors through heatmap and linear regression analysis. Along with basic compartmental modeling, a correlation analysis was performed between the model-estimated parameter values and the discovered effective candidate covariates for levodropropizine, and the degree of toxicity and safety during the clinical trial of levodropropizine was quantitatively monitored, targeting the hepatotoxicity screening panel. As a result, eosinophil level and body surface area (BSA) were explored as significant (p-value < 0.05) physiochemical parameters associated with the pharmacokinetic diversity of levodropropizine. Specifically, it was confirmed that as eosinophil level and BSA increased, levodropropizine plasma exposure increased and decreased, respectively. Interestingly, changes in an individual’s plasma exposure to levodropropizine depending on eosinophil levels could be interpreted as a therapeutic advantage based on pharmacokinetic benefits linked to the clinical indications for levodropropizine. This study presents effective candidate covariates that can explain the inter-individual pharmacokinetic variability of levodropropizine and provides a useful perspective on the first-line choice of levodropropizine in the treatment of inflammatory respiratory diseases.

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