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Metronidazole or Cotrimoxazole therapy is associated with a decrease in intestinal bioavailability of common antiretroviral drugs.

Dossou-Yovo F, Mamadou G, Soudy ID, Limas-Nzouzi N, Miantezila J, Desjeux JF, Eto B - PLoS ONE (2014)

Bottom Line: Transepithelial conductance was reduced after MTZ or CTX in the proximal and distal colon. 3.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Biologie, CNAM, Paris, France.

ABSTRACT
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.

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Mucus thickness of colonic mucus (mean ± SE) after 1 week pre-treatment with 1 mg of Cotrimoxazole (CTX) or 1 mg of Metronidazole (MTZ), compared to control in proximal and distal colon.*P<0.05 and ***P<0.001, n = 24 tissues from 7 rats.
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pone-0089943-g002: Mucus thickness of colonic mucus (mean ± SE) after 1 week pre-treatment with 1 mg of Cotrimoxazole (CTX) or 1 mg of Metronidazole (MTZ), compared to control in proximal and distal colon.*P<0.05 and ***P<0.001, n = 24 tissues from 7 rats.

Mentions: Pre-treatment of animals with antibiotics resulted in an increase in intestinal thickness of mucus in proximal and distal colon (fig. 1 and 2). In the proximal colon, after one week of MTZ or CTX treatment the thickness of mucus was 57.2±8.8 µm and 58.2±6.9 µm, respectively, vs. 43.3±7.6 µm in controls, but the increase was not statistically significant. In the distal colon, it was 121.1±38.4 µm and 170.5±35.0 µm respectively, vs. 40.6±6.9 µm in controls.


Metronidazole or Cotrimoxazole therapy is associated with a decrease in intestinal bioavailability of common antiretroviral drugs.

Dossou-Yovo F, Mamadou G, Soudy ID, Limas-Nzouzi N, Miantezila J, Desjeux JF, Eto B - PLoS ONE (2014)

Mucus thickness of colonic mucus (mean ± SE) after 1 week pre-treatment with 1 mg of Cotrimoxazole (CTX) or 1 mg of Metronidazole (MTZ), compared to control in proximal and distal colon.*P<0.05 and ***P<0.001, n = 24 tissues from 7 rats.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3935968&req=5

pone-0089943-g002: Mucus thickness of colonic mucus (mean ± SE) after 1 week pre-treatment with 1 mg of Cotrimoxazole (CTX) or 1 mg of Metronidazole (MTZ), compared to control in proximal and distal colon.*P<0.05 and ***P<0.001, n = 24 tissues from 7 rats.
Mentions: Pre-treatment of animals with antibiotics resulted in an increase in intestinal thickness of mucus in proximal and distal colon (fig. 1 and 2). In the proximal colon, after one week of MTZ or CTX treatment the thickness of mucus was 57.2±8.8 µm and 58.2±6.9 µm, respectively, vs. 43.3±7.6 µm in controls, but the increase was not statistically significant. In the distal colon, it was 121.1±38.4 µm and 170.5±35.0 µm respectively, vs. 40.6±6.9 µm in controls.

Bottom Line: Transepithelial conductance was reduced after MTZ or CTX in the proximal and distal colon. 3.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Biologie, CNAM, Paris, France.

ABSTRACT
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.

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