PMID- 29872264
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20220330
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 12
DP  - 2018
TI  - Evaluation of the effects of food on levodropropizine controlled-release tablet 
      and its pharmacokinetic profile in comparison to that of immediate-release 
      tablet.
PG  - 1413-1420
LID - 10.2147/DDDT.S146958 [doi]
AB  - BACKGROUND: Levodropropizine is a non-opioid antitussive agent that inhibits 
      cough reflex by reducing the release of sensory peptide in the peripheral region. 
      To improve patients' compliance, a controlled-release (CR) tablet is under 
      development. The aim of this study was to compare the pharmacokinetic (PK) 
      profiles of the CR and immediate-release (IR) tablets of levodropropizine. In 
      addition, the effect of food on the PK properties of levodropropizine CR tablet 
      in healthy subjects was evaluated. SUBJECTS AND METHODS: A randomized, 
      open-label, multiple-dose, three-treatment, three-period, six-sequence, crossover 
      study was conducted on 47 healthy subjects. All subjects were randomly assigned 
      to one of the six sequences, which involve combinations of the following three 
      treatments: levodropropizine IR 60 mg three times in the fasted state (R), 
      levodropropizine CR 90 mg two times in the fasted state (T), and levodropropizine 
      CR 90 mg two times in the fed state (TF). Serial blood samples were collected up 
      to 24 h after the first dose. Tolerability was assessed based on the vital signs, 
      adverse events (AEs), and clinical laboratory tests. RESULTS: Levodropropizine CR 
      showed lower maximum drug concentration (C(max)) and similar total exposure 
      compared to levodropropizine IR. The geometric mean ratios (GMRs) (90% confidence 
      intervals [CIs]) of T to R for the C(max) and area under the concentration-time 
      curve from the 0 to 24 h time points (AUC(0-24h)) were 0.80 (0.75-0.85) and 0.89 
      (0.86-0.93), respectively. In the fed group, levodropropizine CR showed exposure 
      similar to that in the fasted group. The GMRs (90% CIs) of TF to T for the C(max) 
      and AUC(0-24h) were 0.90 (0.85-0.97) and 1.10 (1.05-1.14), respectively. No 
      serious AEs occurred with both levodropropizine CR and IR tablets. CONCLUSION: 
      Total systemic exposure for levodropropizine was similar in subjects receiving 
      the CR and IR formulations in terms of the AUC. Although food delayed the 
      absorption of levodropropizine CR, systemic exposure was not affected.
FAU - Lee, Soyoung
AU  - Lee S
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
FAU - Nam, Kyu-Yeol
AU  - Nam KY
AD  - College of Pharmacy, Ajou University, Suwon, Republic of Korea.
AD  - Korea United Pharm Inc., Seoul, Republic of Korea.
FAU - Oh, Jaeseong
AU  - Oh J
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
FAU - Lee, SeungHwan
AU  - Lee S
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
FAU - Cho, Sang-Min
AU  - Cho SM
AD  - Korea United Pharm Inc., Seoul, Republic of Korea.
FAU - Choi, Youn-Woong
AU  - Choi YW
AD  - Korea United Pharm Inc., Seoul, Republic of Korea.
FAU - Cho, Joo-Youn
AU  - Cho JY
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      College of Medicine and Hospital, Seoul, Republic of Korea.
FAU - Lee, Beom-Jin
AU  - Lee BJ
AD  - College of Pharmacy, Ajou University, Suwon, Republic of Korea.
AD  - Institute of Pharmaceutical Science and Technology, Ajou University, Suwon, 
      Republic of Korea.
FAU - Hong, Jang Hee
AU  - Hong JH
AD  - Department of Pharmacology, Chungnam National University Hospital and College of 
      Medicine, Daejeon, Republic of Korea.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20180523
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Propylene Glycols)
RN  - 0 (Tablets)
RN  - U0K8WHL37U (dipropizine)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Cross-Over Studies
MH  - Drug Tolerance
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Propylene Glycols/administration & dosage/blood/*pharmacokinetics
MH  - Tablets/administration & dosage/pharmacokinetics
MH  - Young Adult
PMC - PMC5973308
OTO - NOTNLM
OT  - controlled-release
OT  - food effect
OT  - immediate-release
OT  - pharmacokinetics
COIS- Disclosure Kyu-Yeol Nam, Sang-Min Cho and Youn-Woong Choi are employees of Korea 
      United Pharm Inc., Seoul, Republic of Korea. The authors report no other 
      conflicts of interest in this work.
EDAT- 2018/06/07 06:00
MHDA- 2018/12/12 06:00
PMCR- 2018/05/23
CRDT- 2018/06/07 06:00
PHST- 2018/06/07 06:00 [entrez]
PHST- 2018/06/07 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/05/23 00:00 [pmc-release]
AID - dddt-12-1413 [pii]
AID - 10.2147/DDDT.S146958 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2018 May 23;12:1413-1420. doi: 10.2147/DDDT.S146958. 
      eCollection 2018.