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

Area of Science:

• Pharmacology
• Gastroenterology
• Infectious Diseases

Background:

• Metronidazole (MTZ) and Cotrimoxazole (CTX) are commonly prescribed antibiotics for HIV/AIDS patients initiating antiretroviral therapy (ART).
• Understanding drug-drug interactions, particularly the impact of antibiotics on ART bioavailability, is crucial for optimizing treatment outcomes in this vulnerable population.

Purpose of the Study:

• To investigate the effects of pre-treatment with MTZ and CTX on the intestinal bioavailability of Atazanavir (ATV) and Ritonavir (RTV) in an animal model.
• To assess changes in colonic mucus thickness, permeability, and active drug transport following antibiotic administration.

Main Methods:

• Rats were orally administered MTZ and CTX for seven days.
• Colonic mucosa was analyzed for mucus layer thickness.
• Ussing chambers were employed to measure net transepithelial fluxes (Jnet) of ATV and RTV.

Main Results:

• Antibiotic treatment significantly increased mucus thickness in both proximal and distal colon.
• Transepithelial conductance, a measure of passive permeability, was reduced post-antibiotic exposure.
• Net secretion of ATV and RTV by the colonic epithelium was significantly increased following MTZ and CTX administration.

Conclusions:

• Pre-treatment with MTZ and CTX leads to an enlarged mucus layer and decreased passive permeability in the rat colon.
• The colonic epithelium actively secretes ATV and RTV after antibiotic therapy, suggesting impaired intestinal bioavailability.
• These findings highlight potential pharmacokinetic challenges when co-administering these antibiotics with specific antiretrovirals.