PMID- 29066863
OWN - NLM
STAT- MEDLINE
DCOM- 20180723
LR  - 20220718
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 11
DP  - 2017
TI  - Pharmacokinetic and safety evaluation of MB12066, an NQO1 substrate.
PG  - 2719-2725
LID - 10.2147/DDDT.S142339 [doi]
AB  - OBJECTIVE: This study evaluated the pharmacokinetics (PKs) and safety of a newly 
      developed beta-lapachone (MB12066) tablet, a natural NAD(P)H:quinone oxidoreductase 
      1 (NQO1) substrate, in healthy male volunteers. METHODS: In a randomized, 
      double-blind, multiple-dose, two-treatment study, 100 mg MB12066 or placebo was 
      given twice daily for 8 days to groups of eight or three fasted healthy male 
      subjects, respectively, followed by serial blood sampling. Plasma concentrations 
      for beta-lapachone were determined using liquid chromatography-tandem mass 
      spectrometry. PK parameters were obtained with non-compartmental analysis. 
      Tolerability was assessed based on physical examinations, vital signs, clinical 
      laboratory tests, and electrocardiograms. RESULTS: Following a single 100 mg 
      MB12066 oral dose, maximum plasma concentration (C(max)) of beta-lapachone was 
      3.56+/-1.55 ng/mL, and the median (range) time to reach C(max) was 3 h (2-5 h). 
      After the 8 days of 100 mg twice daily repeated dosing was completed, mean 
      terminal half-life was determined to be 18.16+/-3.14 h, and the mean area under the 
      plasma concentration vs time curve at steady state was 50.44+/-29.68 ng.h/mL. 
      Accumulation index was 2.72+/-0.37. No serious adverse events (AEs) were reported, 
      and all reported intensities of AEs were mild. CONCLUSION: The results 
      demonstrated that MB12066 was safe and well tolerated in healthy volunteers and 
      that there were no serious AEs. Accumulation in plasma with twice-daily 
      administration was associated with a 2.72 accumulation ratio.
FAU - Lee, Hae Won
AU  - Lee HW
AD  - Clinical Trial Center, Kyungpook National University Hospital.
FAU - Seong, Sook Jin
AU  - Seong SJ
AD  - Clinical Trial Center, Kyungpook National University Hospital.
FAU - Ohk, Boram
AU  - Ohk B
AD  - Clinical Trial Center, Kyungpook National University Hospital.
AD  - Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program 
      for Creative Talent, Kyungpook National University Graduate School.
FAU - Kang, Woo Youl
AU  - Kang WY
AD  - Clinical Trial Center, Kyungpook National University Hospital.
AD  - Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program 
      for Creative Talent, Kyungpook National University Graduate School.
FAU - Gwon, Mi-Ri
AU  - Gwon MR
AD  - Clinical Trial Center, Kyungpook National University Hospital.
FAU - Kim, Bo Kyung
AU  - Kim BK
AD  - Clinical Trial Center, Kyungpook National University Hospital.
AD  - Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program 
      for Creative Talent, Kyungpook National University Graduate School.
FAU - Kim, Hyun-Ju
AU  - Kim HJ
AD  - Cell and Matrix Research Institute, Daegu, Republic of Korea.
FAU - Yoon, Young-Ran
AU  - Yoon YR
AD  - Clinical Trial Center, Kyungpook National University Hospital.
AD  - Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program 
      for Creative Talent, Kyungpook National University Graduate School.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170913
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Naphthoquinones)
RN  - 0 (Tablets)
RN  - 6N4FA2QQ6A (beta-lapachone)
RN  - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone))
RN  - EC 1.6.5.2 (NQO1 protein, human)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Area Under Curve
MH  - Chromatography, Liquid
MH  - Double-Blind Method
MH  - Half-Life
MH  - Humans
MH  - Male
MH  - NAD(P)H Dehydrogenase (Quinone)/*metabolism
MH  - Naphthoquinones/*administration & dosage/adverse effects/pharmacokinetics
MH  - Tablets
MH  - Tandem Mass Spectrometry
MH  - Young Adult
PMC - PMC5604554
OTO - NOTNLM
OT  - MB12066
OT  - healthy volunteers
OT  - pharmacokinetics
OT  - safety
OT  - beta-lapachone
COIS- Disclosure The authors report no conflicts of interest in this work.
EDAT- 2017/10/27 06:00
MHDA- 2018/07/24 06:00
PMCR- 2017/09/13
CRDT- 2017/10/26 06:00
PHST- 2017/10/26 06:00 [entrez]
PHST- 2017/10/27 06:00 [pubmed]
PHST- 2018/07/24 06:00 [medline]
PHST- 2017/09/13 00:00 [pmc-release]
AID - dddt-11-2719 [pii]
AID - 10.2147/DDDT.S142339 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2017 Sep 13;11:2719-2725. doi: 10.2147/DDDT.S142339. 
      eCollection 2017.