Design,<i>in vitro</i>release characterization and pharmacokinetics of novel controlled release pellets containing levodropropizine

Cao, Qing-Ri; Piao, Yong-Nan; Choi, Jae-Seung; Liu, Yan; Yang, Mingshi; Cui, Jing‐Hao

doi:10.3109/10837450.2013.778871

Cited by 6 publications

(6 citation statements)

References 27 publications

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“…C max was 452 ± 203 ng/mL (mean ± SD) and T max was very short at 0.6 ± 0.3 h (mean ± SD). This suggested rapid oral absorption of levodropropizine, consistent with previous reports [ 8 , 11 , 12 , 13 , 14 ]. T 1/2 was 2.3 ± 0.5 h (mean ± SD), mean residence time (MRT) was 3.2 ± 0.6 h (mean ± SD), and clearance (CL/F) was 69 ± 26 L/h (mean ± SD), suggesting rapid and extensive elimination of levodropropizine from the body.…”

Section: Resultssupporting

confidence: 92%

“…The pharmacokinetic results identified in this study were not largely different compared to previous reports [ 11 , 12 , 13 , 14 ]. For example, according to a recent report, the mean values of AUC 0-inf , T 1/2 , and T max following oral administration of immediate-release levodropropizine tablet (60 mg, in fasted state) were 969.06 h·ng/mL, 2.30 h, and 0.75 h, respectively, which were similar to the values of 1000 h·ng/mL, 2.3 h, and 0.6 h determined in this study.…”

Section: Discussioncontrasting

confidence: 72%

“…Therefore, the clinical protocol design for this pharmacokinetic study set the sampling time after administration to 12 h, which is more than four times the T 1/2 . And based on reports that the T max of levodropropizine is approximately within 0.25–2 h [ 8 , 11 , 12 , 13 , 14 ], more than 50% of all sampling points were tightly (at intervals of 10 to 30 min) set within 2 h after administration. This was to properly capture peak levodropropizine concentration in plasma (C max ) and T max due to the expected rapid oral absorption of levodropropizine.…”

Section: Resultsmentioning

confidence: 99%

“…A precision medicine approach is important to optimize cough treatment with levodropropizine, and a key step toward this is the exploration of effective covariates that can account for inter-individual pharmacokinetic variations. To date, levodropropizine clinical studies have primarily focused on the bioequivalence of generic or test formulations [ 11 , 12 , 13 , 14 ], with only one considering its pharmacokinetic parameters in relation to food intake [ 8 ]. For instance, a report by Jang et al [ 11 ] primarily interpreted existing datasets (without exploring hidden covariate factors), providing a narrow scope of pharmacokinetic analysis.…”

Section: Introductionmentioning

confidence: 99%

“…For instance, a report by Jang et al [ 11 ] primarily interpreted existing datasets (without exploring hidden covariate factors), providing a narrow scope of pharmacokinetic analysis. 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 ].…”

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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