PMID- 26095588
OWN - NLM
STAT- MEDLINE
DCOM- 20160622
LR  - 20181113
IS  - 1873-6823 (Electronic)
IS  - 0741-8329 (Print)
IS  - 0741-8329 (Linking)
VI  - 49
IP  - 6
DP  - 2015 Sep
TI  - Oral delivery of ivermectin using a fast dissolving oral film: Implications for 
      repurposing ivermectin as a pharmacotherapy for alcohol use disorder.
PG  - 553-9
LID - S0741-8329(15)20272-8 [pii]
LID - 10.1016/j.alcohol.2015.03.006 [doi]
AB  - Individuals suffering from an alcohol-use disorder (AUD) constitute a major 
      health concern. Preclinical studies in our laboratory show that acute and chronic 
      intraperitoneal (i.p.) administration of ivermectin (IVM) reduces alcohol intake 
      and preference in mice. To enable clinical investigation to use IVM for the 
      treatment of an AUD, development of an oral formulation that can be used in 
      animals as well as long-term preclinical toxicology studies are required. The 
      present work explores the use of a promising alternative dosage form of IVM, 
      fast-dissolving oral films (Cure Pharmaceutical(R)), to test the efficacy and 
      safety of oral IVM in conjunction with alcohol exposure. We tested the effect of 
      IVM (0.21 mg) using a fast-dissolving oral film delivery method on reducing 10% 
      v/v alcohol (10E) intake in female C57BL/6 mice using a 24-h access two-bottle 
      choice paradigm for 6 weeks (5 days per week). Differences in ethanol intake, 
      preference for ethanol, water intake, fluid intake, food intake, changes in mouse 
      and organ weights, as well as histological changes to kidney, liver, and brain 
      were analyzed. The IVM group drank significantly less ethanol over the 30-day 
      period compared to the placebo (blank strip) and the no-treatment groups. Organ 
      weights did not differ between the groups. Histological evaluation showed no 
      differences in the brain and kidney between groups. In the liver, there was a 
      slight increase in the incidence of microvesicular fatty and degenerative changes 
      of the animals receiving the thin strips. No overt hepatocellular necrosis or 
      perivascular inflammation was noted. Overall, these data support the use of this 
      novel method of oral drug delivery for longer-term studies and should facilitate 
      FDA required preclinical testing that is necessary to repurpose IVM for treatment 
      of an AUD.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Yardley, Megan M
AU  - Yardley MM
AD  - Department of Psychology, University of California, Los Angeles, CA 90095, USA.
FAU - Huynh, Nhat
AU  - Huynh N
AD  - Titus Family Department of Clinical Pharmacy and Pharmaceutical Economics and 
      Policy, School of Pharmacy, University of Southern California, 1985 Zonal Ave., 
      Los Angeles, CA 90033, USA.
FAU - Rodgers, Kathleen E
AU  - Rodgers KE
AD  - Titus Family Department of Clinical Pharmacy and Pharmaceutical Economics and 
      Policy, School of Pharmacy, University of Southern California, 1985 Zonal Ave., 
      Los Angeles, CA 90033, USA.
FAU - Alkana, Ronald L
AU  - Alkana RL
AD  - Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, 
      University of Southern California, 1985 Zonal Ave., Los Angeles, CA 90033, USA.
FAU - Davies, Daryl L
AU  - Davies DL
AD  - Titus Family Department of Clinical Pharmacy and Pharmaceutical Economics and 
      Policy, School of Pharmacy, University of Southern California, 1985 Zonal Ave., 
      Los Angeles, CA 90033, USA. Electronic address: ddavies@usc.edu.
LA  - eng
GR  - TL1TR000132/TR/NCATS NIH HHS/United States
GR  - R01 AA022448/AA/NIAAA NIH HHS/United States
GR  - TL1 TR000132/TR/NCATS NIH HHS/United States
GR  - UL1TR000130/TR/NCATS NIH HHS/United States
GR  - AA022448/AA/NIAAA NIH HHS/United States
GR  - UL1 TR000130/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150529
PL  - United States
TA  - Alcohol
JT  - Alcohol (Fayetteville, N.Y.)
JID - 8502311
RN  - 70288-86-7 (Ivermectin)
SB  - IM
MH  - Administration, Oral
MH  - Alcohol Drinking/*drug therapy/pathology/psychology
MH  - Alcohol-Related Disorders/*drug therapy/pathology/psychology
MH  - Animals
MH  - Drug Delivery Systems/*methods
MH  - Drug Repositioning/*methods
MH  - Female
MH  - Ivermectin/*administration & dosage
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Solubility
PMC - PMC4554813
MID - NIHMS695642
OTO - NOTNLM
OT  - Alcoholism therapy
OT  - Drug delivery
OT  - Drug repositioning
OT  - Medications development
COIS- DLD is an inventor on a patent for the use of IVM for the treatment of 
      alcohol-use disorders. The authors have no other conflict of interest and are 
      entirely responsible for the scientific content of the paper.
EDAT- 2015/06/23 06:00
MHDA- 2016/06/23 06:00
PMCR- 2016/09/01
CRDT- 2015/06/23 06:00
PHST- 2015/01/30 00:00 [received]
PHST- 2015/03/23 00:00 [revised]
PHST- 2015/03/26 00:00 [accepted]
PHST- 2015/06/23 06:00 [entrez]
PHST- 2015/06/23 06:00 [pubmed]
PHST- 2016/06/23 06:00 [medline]
PHST- 2016/09/01 00:00 [pmc-release]
AID - S0741-8329(15)20272-8 [pii]
AID - 10.1016/j.alcohol.2015.03.006 [doi]
PST - ppublish
SO  - Alcohol. 2015 Sep;49(6):553-9. doi: 10.1016/j.alcohol.2015.03.006. Epub 2015 May 
      29.