PMID- 23351597
OWN - NLM
STAT- MEDLINE
DCOM- 20130404
LR  - 20190608
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
VI  - 51
IP  - 2
DP  - 2013 Feb
TI  - Relative bioavailability of levodropropizine 60 mg capsule and syrup formulations 
      in healthy male Korean volunteers: a singledose, randomized-sequence, open-label, 
      two-way crossover study.
PG  - 152-60
AB  - BACKGROUND: Levodropropizine is an oral non-opioid anti-tussive drug used in 
      treatment of cough. A new generic 60 mg capsule formulation of levodropropizine 
      has recently been developed. OBJECTIVES: The aim of this study was to assess the 
      pharmacokinetics and bioequivalence of the test (capsule) formulation and 
      reference (syrup) formulation of levodropropizine (60 mg) in healthy, fasted, 
      male Korean volunteers. METHODS: This was a single-dose, randomized sequence, 
      open-label, 2-period crossover study conducted in healthy male Korean volunteers 
      in the fasted state at Kyung Hee University Medical Center (Seoul, Republic of 
      Korea). A single oral dose of the test or reference formulation was followed by a 
      1-week washout period, after which subjects received the alternative formulation. 
      Blood samples were collected at 0 (predose), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 
      4, 6, 8, and 12 hours after study drug administration. Plasma concentration of 
      levodropropizine was determined using a validated liquid chromatography tandem 
      mass spectrometry (LCMS/ MS) method. The formulations were considered 
      bioequivalent if the 90% CIs for C(max), AUC(0-12h) and AUC(0-infinity) were within the 
      predetermined bioequivalence range (80 - 125%, according to the guidelines of the 
      Korea Food and Drug Administration (Korea FDA)). Tolerability was evaluated 
      throughout the study based on vital sign measurements, laboratory analysis (blood 
      biochemistry, hematology, hepatic function and urinalysis) and subject interviews 
      concerning adverse events (AEs). RESULTS: A total of 36 male Korean subjects 
      (mean (SD) age, 23.9 (2.4) years (range 19 - 30 years); height, 176.2 (6.1) cm 
      (range 161 - 190 cm); weight, 69.8 (9.1) kg (range 54.0 - 92.2 kg); body mass 
      index, 22.4 (2.1) kg/m2 (range 19.1 - 28.3 kg/m2)) was enrolled and completed the 
      study. The mean values for C(max), t(max), AUC(0-12h), and AUC(0-infinity) with the test 
      formulation of levodropropizine were 331.51 ng/ml, 0.60 hours, 784.32 ngxh/ml, 
      and 825.82 ngxh/ml, respectively; for the reference formulation, the values were 
      332.81 ng/ml, 0.44 hours, 726.46 ngxh/ml, and 769.46 ngxh/ ml, respectively. The 
      90% CIs for the logtransformed ratios of C(max) (92.74 - 111.24), AUC(0-12h) 
      (104.31 - 113.67) and AUC(0-infinity) (103.87 - 113.57) were within the predetermined 
      range for the assumption of bioequivalence. No serious adverse events were 
      reported. CONCLUSIONS: This single-dose (60 mg) study found that the test 
      (capsule) and reference (syrup) formulations of levodropropizine met the 
      regulatory criterion for assuming bioequivalence in these healthy, fasted, male 
      Korean subjects. Both formulations were well tolerated in the population studied. 
      Korea FDA registration number: BED-1784.
FAU - Jang, Jae-Won
AU  - Jang JW
AD  - Department of Pharmaceutical Biochemistry, College of Pharmacy, College of 
      Medical Science, Kyung Hee University, Seoul, Republic of Korea.
FAU - Seo, Ji-Hyung
AU  - Seo JH
FAU - Jo, Min-Ho
AU  - Jo MH
FAU - Lee, Young-Joo
AU  - Lee YJ
FAU - Cho, Young-Wuk
AU  - Cho YW
FAU - Yim, Sung-Vin
AU  - Yim SV
FAU - Lee, Kyung-Tae
AU  - Lee KT
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
RN  - 0 (Antitussive Agents)
RN  - 0 (Capsules)
RN  - 0 (Propylene Glycols)
RN  - U0K8WHL37U (dipropizine)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Analysis of Variance
MH  - Antitussive Agents/*administration & dosage/blood/*pharmacokinetics
MH  - Area Under Curve
MH  - Biological Availability
MH  - Capsules
MH  - Chromatography, Liquid/methods
MH  - Cross-Over Studies
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Propylene Glycols/*administration & dosage/blood/*pharmacokinetics
MH  - Republic of Korea
MH  - Tandem Mass Spectrometry/methods
MH  - Young Adult
EDAT- 2013/01/29 06:00
MHDA- 2013/04/05 06:00
CRDT- 2013/01/29 06:00
PHST- 2013/01/29 06:00 [entrez]
PHST- 2013/01/29 06:00 [pubmed]
PHST- 2013/04/05 06:00 [medline]
AID - 10383 [pii]
AID - 10.5414/cp201730 [doi]
PST - ppublish
SO  - Int J Clin Pharmacol Ther. 2013 Feb;51(2):152-60. doi: 10.5414/cp201730.