Pharmacokinetics and Safety of Levodropropizine Controlled Release Tablet after Repeated Dosing in Healthy Male Volunteers
Background: Levodropropizine is non-opioid agent whose peripheral antitussive action may result from
its modulation of sensory neuropeptide levels. Currently, levodropropizine 60 mg is taken three-times daily.
A controlled release formulation of levodropropizine (levodropropizine CR) 90 mg was developed, which
can be taken twice daily. The aim of this study was to evaluate the safety and pharmacokinetic
characteristics after multiple oral administrations of levodropropizine CR 90 mg tablets in healthy male
Methods: A randomized, open-label, cross-over study was conducted in 24 healthy male volunteers. Each
subject received levodropropizine syrup 60 mg three times daily or levodropropizine CR 90 mg twice daily
for 3 days. Blood samples for pharmacokinetic analysis were collected pre-dose and up to 24 hours on
day 4. Pharmacokinetic analysis was conducted by non-compartmental method. Safety assessments
including monitoring adverse events, laboratory tests, vital signs, physical examinations and ECGs were
performed throughout the study.
Results: A total of 20 male volunteers completed the study. The maximum steady-state plasma
concentration (Css,max) of levodropropizine syrup and levodropropizine CR were 313.28 ng/mL and 285.31
ng/mL and time to reach Css,max (Tmax,ss) were 0.48 hr and 0.88 hr, respectively. The area under the
concentration-time curve to the last measured concentration of two groups were 2345.36 hr × ng/mL and
2553.81 hr × ng/mL, respectively. There was no serious adverse event.
Conclusion: Levodropropizine CR 90 mg tablet was safe and well-tolerated when administered twice daily
for 3 days. No statistically significant differences were seen in Css,max and AUCss,24hr between the two
formulations. This study provided pharmacokinetic evidences that the twice-daily dosing regimen of
levodropropizine 90 mg may substitute the conventional 3-times-daily regimen of levodropropizine 60 mg.