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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Metronidazole or cotrimoxazole therapy is associated with a decrease in intestinal bioavailability of common antiretroviral drugs
PLoS ONE, Volume 9, No. 2, Article e89943, Year 2014
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Description
Metronidazole (MTZ) and Cotrimoxazole (CTX) are used in HIV/AIDS patients eligible for antiretroviral treatment. The objective of this animal study was to determine whether pre-treatment with antibiotics affects the intestinal bioavailability of Atazanavir (ATV) and Ritonavir (RTV). After oral administration of 1 mg MTZ and CTX for 7 days, the rat colonic mucosa were analyzed for mucus thickness or placed in Ussing chambers to measure ATV and RTV net transepithelial fluxes (Jnet). 1. In control rats, the mucus thickness was 43.3±7.6 μm and 40.7±6.9 μm, in proximal and distal colon, respectively. In proximal colon, the thickness was 57.2±8.8 and 58.2±6.9 μm after MTZ and CTX, respectively whereas in distal colon, the thickness was 121.1±38.4 and 170.5±35.0 μm (P<0.05) respectively. 2. Transepithelial conductance was reduced after MTZ or CTX in the proximal and distal colon. 3. In control, net ATV secretion was observed both in proximal (-0.36±0.02 μg.hr-1 cm -2) and distal colon (-0.30±0.08 μg.hr-1 cm -2). After MTZ and CTX, it was increased in the proximal colon by two 2 fold and 4 fold, respectively and in the distal colon by 3 fold and 5 fold, respectively. 4. In control, there was no net active RTV transport either in proximal (+0.01±0.01 μg.hr-1 cm-2) or distal colon (+0.04±0.01 μg.hr-1 cm-2). After MTZ and CTX, secretion was increased 5 fold and 10 fold, respectively, in the proximal colon and two fold and 5 fold, respectively in the distal colon (p<0.001). In conclusion, after MTZ and CTX therapy, the mucus layer was enlarged, passive permeability was decreased and ATV and RTV were actively secreted by the colonic epithelium suggesting that, in rat, the intestinal bioavailability of ATV and RTV is impaired after antibiotic therapy. © 2014 Dossou-Yovo et al.
Authors & Co-Authors
Dossou-Yovo, Flore
France, Paris
Conservatoire National Des Arts et Metiers
Mamadou, Godefroy
France, Paris
Université Paris Cité
Soudy, Imar Djibrine
France, Paris
Université Paris Cité
Chad
Institut Universitaire Des Sciences et Technique D'abéché
Limas-Nzouzi, Nicolas
France, Paris
Université Paris Cité
Miantezila, Joe
France, Paris
Université Paris Cité
Desjeux, Jehan François
France, Paris
Academie Nationale de Médecine
Eto, B.
France, Paris
Université Paris Cité
Statistics
Citations: 16
Authors: 7
Affiliations: 4
Identifiers
Doi:
10.1371/journal.pone.0089943
e-ISSN:
19326203
Research Areas
Health System And Policy
Infectious Diseases