Levodropropizine

Acute post-viral cough is a common symptom, usually mild-moderate and self-resolving. However, acute cough may be particularly annoying, affecting sleep, and quality of life, also of the family. Thus, treatment is deemed necessary. Antitussive remedies may be pharmacological or non-pharmacological. Antitussive drugs are either central or peripheral. Central drugs are burdened with significant side effects and can cause abuse, especially in adolescents. Levodropropyzine, on the other hand, is an effective peripheral drug, as demonstrated by two meta-analyses, and has an optimal safety profile. Non-pharmacological remedies tend to be safe, but few substances have a documented degree of efficacy. Therefore, when managing children and adolescents with a post-viral cough, the practical approach may be based on levodropropizine use, which is preferable when the cough is particularly persistent and disturbs sleep.

Levodropropizine, a nonopioid antitussive agent, is being increasingly used in clinical practice with the development of several formulations for symptomatic relief of acute and chronic bronchitis. However, scientific and quantitative population pharmacokinetic analyses of levodropropizine are lacking. Moreover, no integrated quantitative comparison has been performed between formulations. This study quantitatively evaluated and predicted pharmacokinetic properties of formulations through population pharmacokinetic model-based comparisons of commercially available formulations. Plasma concentration profile results from bioequivalence studies of 60-mg immediate release (IR) levodropropizine tablets in 40 healthy Korean males were used as population pharmacokinetic modeling data. For interindividual variability in levodropropizine pharmacokinetics, body surface area was identified as an effective covariate that was positively correlated with peripheral compartment distribution volume. Population pharmacokinetic model for IR tablets well-described the levodropropizine syrup and capsule datasets, suggesting no significant differences in pharmacokinetics among IR tablets, syrups, and capsules of levodropropizine. In contrast, pharmacokinetic profiles differed between 90-mg controlled release (CR) and IR levodropropizine tablets; however, separate parameter estimation was possible by applying the same model structure. In terms of pharmacokinetics, twice-daily regimen of 90-mg CR tablets was equivalent to thrice-daily regimen of 60-mg IR tablets. However, at steady-state, interindividual plasma concentration variability within population was reduced by approximately 36.71-83.18%. For levodropropizine CR tablets, a high-fat diet significantly delayed gastrointestinal absorption but maintained overall plasma exposure equivalent. This study provides useful quantitative judgment data for precision medicine of levodropropizine and can be helpful in predicting the pharmacokinetics of levodropropizine based on commercialized formulation switching.