Development of rectal enema as microbicide (DREAM): Preclinical progressive selection of a tenofovir prodrug enema.

Adenine / analogs & derivatives Administration, Rectal Alanine Animals Anti-HIV Agents / pharmacology Anti-Infective Agents / pharmacology Enema / methods HIV Infections / drug therapy HIV-1 / drug effects Homosexuality, Male Male Mice Organophosphates / pharmacology Organophosphonates / pharmacology Pre-Exposure Prophylaxis / methods Prodrugs / pharmacology Rectum / drug effects Sexual and Gender Minorities Tenofovir / pharmacology
Fleet Hypotonic Rectal douche Rectal gel Sodium bicarbonate

Journal

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
ISSN: 1873-3441
Titre abrégé: Eur J Pharm Biopharm
Pays: Netherlands
ID NLM: 9109778

Informations de publication

Date de publication:
May 2019
Historique:
received: 11 04 2018
revised: 14 05 2018
accepted: 22 05 2018
pubmed: 29 5 2018
medline: 15 8 2019
entrez: 27 5 2018
Statut: ppublish

Résumé

HIV pre-exposure prophylaxis (PrEP) strategies have the potential to prevent millions of incident HIV infections each year. However, the efficacy of PrEP strategies has been plagued by issues of non-adherence, likely because of the difficulty in motivating otherwise healthy people to adhere to treatment regimens that require significant behavioral changes and daily discipline. An alternative approach to PrEP is to focus on strategies that fit in to normal, and even desirable, sexual behaviors, such as the use of cleansing enemas by men who have sex with men (MSM) prior to receptive anal intercourse (RAI). Here, we describe preclinical efforts toward optimizing a tenofovir (TFV)-based enema formulation for rectal PrEP. Using a murine model, we compared the plasma and tissue pharmacokinetics of TFV and various TFV prodrugs, including tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and hexadecyloxypropyl tenofovir (CMX157), after dosing as enema formulations with varying osmolality and ion content. We observed that the enema vehicle composition played a more important role than the TFV prodrug properties in achieving rapid and therapeutically relevant tenofovir diphosphate (TFV-DP) concentrations in mouse colorectal tissue. Our results support the next steps, which are further preclinical (non-human primate) and clinical development of a hypo-osmolar TFV enema product for rectal PrEP.

Identifiants

DOI: 10.1016/j.ejpb.2018.05.030 PMID: 29802984 PMC: PMC6428633
pubmed: 29802984
pii: S0939-6411(18)30476-4
doi: 10.1016/j.ejpb.2018.05.030
pmc: PMC6428633
mid: NIHMS1013344
pii:
doi:

Substances chimiques

Anti-HIV Agents 0
Anti-Infective Agents 0
Organophosphates 0
Organophosphonates 0
Prodrugs 0
tenofovir diphosphate 0
Tenofovir 99YXE507IL
tenofovir alafenamide EL9943AG5J
Adenine JAC85A2161
hexadecyloxypropyl 9-(2-(phosphonomethoxy)propyl)adenine K7J545MEMA
Alanine OF5P57N2ZX

Types de publication

Journal Article

Langues

eng

Pagination

23-29

Subventions

Organisme : NIGMS NIH HHS
ID : P20 GM103466
Pays : United States
Organisme : NIMHD NIH HHS
ID : U54 MD007601
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107806
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM113134
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI113127
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI094189
Pays : United States
Organisme : NIH HHS
ID : P51 OD011132
Pays : United States

Informations de copyright

Copyright © 2018 Elsevier B.V. All rights reserved.

Références

Gut. 1998 Aug;43(2):294-9
pubmed: 10189861
Antimicrob Agents Chemother. 2001 Oct;45(10):2733-9
pubmed: 11557462
Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):1091-8
pubmed: 11562963
Antimicrob Agents Chemother. 2005 May;49(5):1898-906
pubmed: 15855512
Sex Transm Dis. 2010 Apr;37(4):228-33
pubmed: 19959973
Int J Epidemiol. 2010 Aug;39(4):1048-63
pubmed: 20406794
Antimicrob Agents Chemother. 2010 Jul;54(7):2901-9
pubmed: 20439609
J Sex Med. 2011 Nov;8(11):3040-50
pubmed: 21883941
AIDS Res Hum Retroviruses. 2012 Nov;28(11):1412-21
pubmed: 22943559
Sci Transl Med. 2012 Sep 12;4(151):151ra125
pubmed: 22972843
AIDS Patient Care STDS. 2013 Feb;27(2):77-84
pubmed: 23373663
PLoS One. 2013;8(1):e55013
pubmed: 23383037
AIDS Res Hum Retroviruses. 2013 Nov;29(11):1443-50
pubmed: 23600365
J Acquir Immune Defic Syndr. 2013 Aug 1;63(4):449-55
pubmed: 23807155
AIDS Res Hum Retroviruses. 2013 Nov;29(11):1487-95
pubmed: 23885722
Cell. 2013 Oct 24;155(3):515-8
pubmed: 24243011
PLoS One. 2014 Oct 28;9(10):e106196
pubmed: 25350119
J Control Release. 2015 Jan 10;197:48-57
pubmed: 25449804
PLoS One. 2015 May 05;10(5):e0125363
pubmed: 25942472
AIDS Res Hum Retroviruses. 2016 Jan;32(1):32-43
pubmed: 26414912
Antimicrob Agents Chemother. 2017 Dec 21;62(1):
pubmed: 29084755
AIDS Behav. 2018 Apr;22(4):1288-1294
pubmed: 29098455
Open Access J Contracept. 2016 May 11;7:89-96
pubmed: 29386940
J Pharmacokinet Biopharm. 1988 Jun;16(3):303-9
pubmed: 3221328
J Clin Invest. 1969 Jul;48(7):1336-47
pubmed: 5794255
Antimicrob Agents Chemother. 1998 Mar;42(3):612-7
pubmed: 9517941

Auteurs

Thuy Hoang (T)

The Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD, USA.

Abhijit A Date (AA)

The Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA.

Jairo Ortiz Ortiz (JO)

The Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA.

Ting-Wei Young (TW)

The Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA.

Sabrine Bensouda (S)

The Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA; Department of Medicine, Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Peng Xiao (P)

New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.

Mark Marzinke (M)

Department of Medicine, Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Lisa Rohan (L)

Department of Pharmaceutical Sciences, University of Pittsburgh and Magee-Womens Research Institute, Pittsburgh, PA, USA.

Edward J Fuchs (EJ)

Department of Medicine, Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Craig Hendrix (C)

Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD, USA; Department of Medicine, Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Sanjeev Gumber (S)

Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.

Francois Villinger (F)

New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.

Richard A Cone (RA)

The Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA; Department of Biophysics, Johns Hopkins University, Baltimore, MD, USA.

Justin Hanes (J)

The Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD, USA. Electronic address: hanes@jhmi.edu.

Laura M Ensign (LM)

The Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD, USA. Electronic address: lensign@jhmi.edu.

Articles similaires

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Meal Timing and Anthropometric and Metabolic Outcomes: A Systematic Review and Meta-Analysis.

Hiu Yee Liu, Ashley A Eso, Nathan Cook et al.
1.00
Humans Meals Time Factors Female Adult

Classifications MeSH

questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Purines › Adénine › Development of rectal enema as microbicide...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Administration par voie topique › Administration par voie muqueuse › Administration par voie rectale › Development of rectal enema as microbicide...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Alanine › Development of rectal enema as microbicide...
questionsmedicales.fr › Eucaryotes › Animaux › Development of rectal enema as microbicide...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiviraux › Antirétroviraux › Agents antiVIH › Development of rectal enema as microbicide...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Development of rectal enema as microbicide...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Lavement (produit) › Development of rectal enema as microbicide...
questionsmedicales.fr › Maladies du système immunitaire › Déficits immunitaires › Infections à VIH › Development of rectal enema as microbicide...
questionsmedicales.fr › Virus › Virus à ARN › Retroviridae › Lentivirus › Lentivirus des primates › VIH (Virus de l'Immunodéficience Humaine) › VIH-1 (Virus de l'Immunodéficience Humaine de type 1) › Development of rectal enema as microbicide...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Sexualité › Homosexualité › Homosexualité masculine › Development of rectal enema as microbicide...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Development of rectal enema as microbicide...
questionsmedicales.fr › Composés chimiques organiques › Composés organiques du phosphore › Organophosphates › Development of rectal enema as microbicide...
questionsmedicales.fr › Composés chimiques organiques › Composés organiques du phosphore › Phosphonates › Development of rectal enema as microbicide...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Pratiques en santé publique › Prévention primaire › Prophylaxie pré-exposition › Development of rectal enema as microbicide...
questionsmedicales.fr › Préparations pharmaceutiques › Promédicaments › Development of rectal enema as microbicide...
questionsmedicales.fr › Système digestif › Tube digestif › Tube digestif inférieur › Gros intestin › Rectum › Development of rectal enema as microbicide...
questionsmedicales.fr › Personnes › Disparités en matière de santé, minorités et populations vulnérables › Minorités sexuelles › Development of rectal enema as microbicide...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Purines › Adénine › Ténofovir › Development of rectal enema as microbicide...