DMD Large equally mixed donor pool

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by van Gelder, J.
Right arrow Articles by Augustijns, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van Gelder, J.
Right arrow Articles by Augustijns, P.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*CYCLOSPORIN A

Vol. 30, Issue 8, 924-930, August 2002

Intestinal Absorption Enhancement of the Ester Prodrug Tenofovir Disoproxil Fumarate through Modulation of the Biochemical Barrier by Defined Ester Mixtures

J. van Gelder, S. Deferme, L. Naesens, E. De Clercq, G. van den Mooter, R. Kinget, and P. Augustijns

Laboratorium voor Farmacotechnologie en Biofarmacie, Campus Gasthuisberg O&N, KULeuven, Belgium (J.v.G., S.D., G.v.d.M., R.K.); and Rega Institute for Medical Research, KULeuven, Belgium (L.N., E.D.C.)

The effect of discrete esters and ester mixtures on the intestinal stability and absorption of tenofovir disoproxil fumarate (tenofovir DF, an esterase-sensitive prodrug of the antiviral tenofovir) was compared with the effect of strawberry extract, which has been shown to enhance the absorption of the prodrug across Caco-2 monolayers and in rat ileum. In addition, the mechanism of absorption enhancement was investigated. In rat intestinal homogenates, complete inhibition of the conversion of tenofovir DF (as obtained by strawberry extract) could only be obtained at relatively high concentrations of the discrete esters or by using mixtures of esters (e.g., propyl p-hydroxybenzoate 0.02%, octyl acetate 0.02%, ethyl caprylate 0.01%). Coincubation of tenofovir DF with this mixture also resulted in an enhancement of its absorption in the in vitro Caco-2 system as well as in rat ileum. As tenofovir DF is a substrate for P-glycoprotein (P-gp)-related efflux carriers in the Caco-2 model, the modulatory effect of the ester mixtures was studied on the functionality of P-gp using cyclosporin A (CsA) as a model substrate. Strawberry extract as well as the mixture of three esters interfered with the absorptive transport of CsA across Caco-2 monolayers, illustrating that both mixtures interfere with both esterase-activity and P-gp functionality. This concerted barrier was not observed in rat ileum, suggesting differential functional activities of the biochemical barrier toward tenofovir DF in different absorption systems. Overall, our results illustrate that modulation of the biochemical barrier (metabolism and efflux) of tenofovir DF by ester mixtures can be used to increase the intestinal absorption of tenofovir DF in an in vitro and an in situ absorption model; the mechanism of action appears to be a complex interplay of different systems; the differential expression of carriers and enzymes in different systems illustrates the difficulty of extrapolating observations between different systems/species.

Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
R. Mols, J. Brouwers, A. H. Schinkel, P. Annaert, and P. Augustijns
INTESTINAL PERFUSION WITH MESENTERIC BLOOD SAMPLING IN WILD-TYPE AND KNOCKOUT MICE: Evaluation of a Novel Tool in Biopharmaceutical Drug Profiling
Drug Metab. Dispos., June 1, 2009; 37(6): 1334 - 1337.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
L. Tong, T. K. Phan, K. L. Robinson, D. Babusis, R. Strab, S. Bhoopathy, I. J. Hidalgo, G. R. Rhodes, and A. S. Ray
Effects of Human Immunodeficiency Virus Protease Inhibitors on the Intestinal Absorption of Tenofovir Disoproxil Fumarate In Vitro
Antimicrob. Agents Chemother., October 1, 2007; 51(10): 3498 - 3504.
[Abstract] [Full Text] [PDF]

Home page
 J Clin PharmacolHome page
I. Ofotokun, S. K. Chuck, J. N. Binongo, M. Palau, J. L. Lennox, and E. P. Acosta
Lopinavir/Ritonavir Pharmacokinetic Profile: Impact of Sex and Other Covariates Following a Change From Twice-Daily to Once-Daily Therapy
J. Clin. Pharmacol., August 1, 2007; 47(8): 970 - 977.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
P. Li, P. S. Callery, L.-S. Gan, and S. K. Balani
Esterase Inhibition Attribute of Grapefruit Juice Leading to a New Drug Interaction
Drug Metab. Dispos., July 1, 2007; 35(7): 1023 - 1031.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
P. Li, P. S. Callery, L.-S. Gan, and S. K. Balani
Esterase Inhibition by Grapefruit Juice Flavonoids Leading to a New Drug Interaction
Drug Metab. Dispos., July 1, 2007; 35(7): 1203 - 1208.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
H. Chanteux, F. Van Bambeke, M.-P. Mingeot-Leclercq, and P. M. Tulkens
Accumulation and Oriented Transport of Ampicillin in Caco-2 Cells from Its Pivaloyloxymethylester Prodrug, Pivampicillin
Antimicrob. Agents Chemother., April 1, 2005; 49(4): 1279 - 1288.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
J. A. H. Droste, C. P. W. G. M. Verweij-van Wissen, B. P. Kearney, R. Buffels, P. J. vanHorssen, Y. A. Hekster, and D. M. Burger
Pharmacokinetic Study of Tenofovir Disoproxil Fumarate Combined with Rifampin in Healthy Volunteers
Antimicrob. Agents Chemother., February 1, 2005; 49(2): 680 - 684.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
A.-M. Taburet, C. Piketty, C. Chazallon, I. Vincent, L. Gerard, V. Calvez, F. Clavel, J.-P. Aboulker, and P.-M. Girard
Interactions between Atazanavir-Ritonavir and Tenofovir in Heavily Pretreated Human Immunodeficiency Virus-Infected Patients
Antimicrob. Agents Chemother., June 1, 2004; 48(6): 2091 - 2096.
[Abstract] [Full Text] [PDF]

Home page
 The Annals of PharmacotherapyHome page
S. A Grim and F. Romanelli
Tenofovir Disoproxil Fumarate
Ann. Pharmacother., June 1, 2003; 37(6): 849 - 859.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2002 by the American Society for Pharmacology and Experimental Therapeutics.