Gastrointestinal permeability studies using combinations of rifampicin and nucleoside analogue reverse transcriptase inhibitors in rats

Objectives: To investigate the gastrointestinal tract (GIT) permeability of five nucleoside analogue reverse transcriptase inhibitors (NRTIs), viz., zidovudine, stavudine, abacavir sulphate, lamivudine and didanosine, individually and in the presence of rifampicin in rats by ligated-loop technique.
Materials and Methods: The permeability studies were carried out on Sprague-Dawley rats in the weight range of 240-260 g. The drug contents were estimated by a validated gradient HPLC method. Degradation and solubility studies were also carried out on the drugs, alone and in combination, to correlate with the results of in situ experiments.
Results: The results showed that rifampicin was better absorbed from stomach and duodenum; zidovudine was moderately absorbed throughout GIT; stavudine and lamivudine were absorbed better through the intestine; abacavir was well absorbed through duodenum; and didanosine completely disappeared through stomach and was absorbed moderately from proximal parts of the intestine. In drug combinations, NRTIs did not influence permeability/absorption of rifampicin and vice versa. The disappearance of didanosine through stomach could be ascribed to decomposition of the drug at pH 2.
Conclusion: The study reaffirms that rifampicin and NRTIs do not influence gastrointestinal permeability of each other.

Keywords
Rifampicin, NRTIs, gastrointestinal permeability, solubility, degradation