PMID- 36819512
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230224
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 11
IP  - 2
DP  - 2023 Jan 31
TI  - Pharmacokinetics and bioequivalence study of montelukast sodium oral soluble film 
      and chewable tablet in healthy Chinese volunteers: randomized trials under 
      fasting and fed conditions.
PG  - 93
LID - 10.21037/atm-22-6485 [doi]
LID - 93
AB  - BACKGROUND: The oral soluble film (OSF) is a new drug delivery system. Whether 
      montelukast sodium OSF has similar pharmacokinetic (PK) properties and 
      bioequivalence to chewable tablet (CT) should be investigated. METHODS: This 
      study, conducted at Haikou People's Hospital, consisted of two trials: a 
      randomized, open-label, single-dose, 3-sequence, 3-period crossover trial under 
      fasting conditions and a randomized, open-label, single-dose, 2-sequence, 
      2-period crossover trial under fed conditions. Healthy volunteers were randomized 
      1:1:1 to receive single-dose oral montelukast sodium OSF without water, OSF, or 
      CT with water in the fasting trial, and 1:1 to receive OSF or CT with water in 
      the fed trial in each period, with a 7-day washout period. Randomization was 
      performed according to random number tables generated using computer. Blood 
      samples were collected over a 24-h period. Plasma drug concentrations were tested 
      using high-performance liquid chromatography-tandem mass spectrometry. The 
      primary PK parameters were maximum plasma drug concentration (C(max)), area under 
      the plasma drug concentration-time curve (AUC) from t=0 to the last quantifiable 
      concentration (AUC(0-t)), and AUC from t=0 to infinity (AUC(0-infinity)). The other PK 
      parameters included time to C(max) (T(max)), terminal elimination rate constant 
      (lambda(z)), and half-life (t(1/2)). Safety was also assessed. Analysis of variance on 
      log-transformed primary PK parameters was applied to analyze the bioequivalence 
      between the OSF and CT. The bioequivalence margin was 80-125%. RESULTS: From 
      November 2018 to January 2019, 30 subjects were included in each trial. The PK 
      parameters between OSF and CT were numerically similar. All 90% confidence 
      intervals (CIs) of the geometric mean ratio (GMR) for the primary PK parameters 
      fell within 80-125%, confirming the bioequivalence of montelukast sodium OSF and 
      CT under fasting and fed conditions. In the fasting trial, 6 (20%) adverse events 
      (AEs) were reported, including 3 (10%) cases after OSF administration without 
      water and 3 (10%) after OSF administration with water, with no serious AEs. No 
      AEs were recorded in the fed trial. CONCLUSIONS: Montelukast sodium OSF is 
      bioequivalent to CT, with acceptable safety. The OSF is an alternative option of 
      CT. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT05528198 (the fasting 
      trial) and NCT05531994 (the fed trial).
CI  - 2023 Annals of Translational Medicine. All rights reserved.
FAU - Zhu, Gangzhi
AU  - Zhu G
AD  - Phase I Clinical Trial Center, Haikou People's Hospital, Haikou, China.
FAU - Wang, Liu
AU  - Wang L
AD  - Phase I Clinical Trial Center, Haikou People's Hospital, Haikou, China.
FAU - Han, Shengnan
AU  - Han S
AD  - Phase I Clinical Trial Center, Haikou People's Hospital, Haikou, China.
FAU - Peng, Hui
AU  - Peng H
AD  - Phase I Clinical Trial Center, Haikou People's Hospital, Haikou, China.
FAU - Tong, Mei
AU  - Tong M
AD  - Phase I Clinical Trial Center, Haikou People's Hospital, Haikou, China.
FAU - Gu, Xingli
AU  - Gu X
AD  - Department of Clinical Research, Qilu Pharmaceutical Co., Ltd., Jinan, China.
FAU - Hu, Haixun
AU  - Hu H
AD  - Department of Clinical Research, Qilu Pharmaceutical Co., Ltd., Jinan, China.
FAU - Wang, Yue
AU  - Wang Y
AD  - Department of Clinical Research, Qilu Pharmaceutical Co., Ltd., Jinan, China.
FAU - Lv, Zhaoguo
AU  - Lv Z
AD  - Department of Clinical Research, Qilu Pharmaceutical Co., Ltd., Jinan, China.
FAU - He, Xiaoai
AU  - He X
AD  - Phase I Clinical Trial Center, Haikou People's Hospital, Haikou, China.
LA  - eng
SI  - ClinicalTrials.gov/NCT05528198
SI  - ClinicalTrials.gov/NCT05531994
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC9929805
OTO - NOTNLM
OT  - Montelukast sodium
OT  - bioequivalence
OT  - oral soluble film (OSF)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://atm.amegroups.com/article/view/10.21037/atm-22-6485/coif). GZ, LW, SH, 
      HP, MT, and XH report that they received funding from Qilu Pharmaceutical Co., 
      Ltd. XG, HH, YW, and ZL are employees of Qilu Pharmaceutical Co., Ltd. The 
      authors have no other conflicts of interest to declare.
EDAT- 2023/02/24 06:00
MHDA- 2023/02/24 06:01
PMCR- 2023/01/31
CRDT- 2023/02/23 10:04
PHST- 2022/12/01 00:00 [received]
PHST- 2023/01/11 00:00 [accepted]
PHST- 2023/02/23 10:04 [entrez]
PHST- 2023/02/24 06:00 [pubmed]
PHST- 2023/02/24 06:01 [medline]
PHST- 2023/01/31 00:00 [pmc-release]
AID - atm-11-02-93 [pii]
AID - 10.21037/atm-22-6485 [doi]
PST - ppublish
SO  - Ann Transl Med. 2023 Jan 31;11(2):93. doi: 10.21037/atm-22-6485.