Effect of Gastrointestinal Infection on the Tissue Distribution and Short Term Kinetics of Radio-iodine Labeled Metronidazole and 2Nitroimdazole in Male Albino Mice.

Specific pathological conditions affect the tissue distribution and kinetics of administered drugs; as they may alter the magnitude and duration of drug content in targeted organs Metronidazole (MET) and 2-Nitroimidazole (2-NIM) possess selective activity against many anaerobic gram-positive and Gram-negative bacteria and protozoa causing gastrointestinal infection. The main aim of the present study was to evaluate the gastrointestinal tissue (GIT) distribution of Metronidazole and 2-Nitroimidazole in Escherichia coli-induced gastrointestinal infection in mice. Sixty male albino mice were divided into four main groups; and each were subdivided into 3 sub-groups of five mice. Two main healthy groups were given i.v injection of (125I-2-NIM or125I-MET) and the other two groups were given 0.2 mL of Escherichia coli (E. coli) via oral route for induction of bacterial gastroenteritis 24 hr. before i.v. injection with (125I-2-NIM or 125I-MET). Each of the sub-groups was sacrificed by decapitation under chloroform anesthesia after i.v. injection of the tracer blood by 30 min., 60min., and 180min. Where blood, GIT, liver tissue samples and urine were collected at the time of decapitation; and the radioactivity was measured using a ?-counter. The uptake was expressed as the percent of injected dose per organ or body fluid. Blood was collected for determining complete blood picture (CBC), and Erythrocyte sedimentation rate (E.S.R) and sera from blood samples were separated for determining evidence of inflammatory response and for assessing the possible effects on hepato-renal function and lipid profile. Data from the present study showed also, that both MET and 2-NIM experienced high blood to tissue perfusion after only 30 min. They also showed that while (MET) continued to leak from the blood to the peripheral tissue over 180 min, (2-NIM), underwent a reversed tissue to blood mobilization after 60 min. MET in infected and non-infected mice experienced a similar but a paradoxical tissue to blood equilibration overtime while 2-NIM demonstrated an initial rise in blood and GIT after 30 min that was followed by a parallel leak from both tissues from 60 min. to180 min. in intact animals. GIT infection enhanced the local perfusion of both medications and this was more pronounced in 2-NIM treated animals. Data also demonstrated that more than 60% of injected 2- NIM tracers were excreted in urine after 180 min while only 20% of injected MET tracer was cleared in urine over the same period suggesting more tissue retention of MET than 2-NIM. In conclusion, the present study heralds’ different tissue distribution kinetics between MET and 2-NIM with more affinity of MET to GIT tissue. They also infer that 2-NIM experiences a higher clearance rate from the body through the urine than MET. Despite MET was more concentrated in the GIT than 2-NIM, the later was more concentrated upon GIT infection than MET.