Paromomycin belongs to the group of aminoglycoside antibiotics. Paromomycin changes the reading of messenger-RNA, which disrupts protein synthesis. The bactericidal activity of paromomycin is mainly attributed to its irreversible binding to ribosomes. Paromomycin has broad spectrum activity against numerous Grampositive and Gram-negative bacteria, including E. coli. Paromomycin acts in a concentration-dependant manner. Five mechanisms of resistance have been identified: changes of the ribosomes due to mutations, reduction of permeability of bacterial cell wall or active efflux, enzymatic modification of ribosomes and inactivation of aminoglycosides by enzymes. The first three resistance mechanisms arise from mutations of certain genes on bacterial chromosome. The fourth and fifth resistance mechanism only occurs following uptake of mobile genetic elements coding for resistance. Paromomycin selects for resistance and cross-resistances at high frequency against a variety of other aminoglycosides among intestinal bacteria. Prevalence of resistance of E. coli to paromomycin was relatively stable between 2002 to 2015 and around 40% for bovine pathogens and 10% for porcine pathogens.

Paromomycin has antiprotozoal activity, although its mechanism of action is unclear. In in vitro studies using HCT-8 and Caco-2 cell lines inhibitory activity against C. parvum was observed. Resistance of cryptosporidia to paromomycin has not been described to date. Nevertheless, the use of aminoglycosides is associated with the occurrence of bacterial resistance. Paromomycin may select for cross-resistance to other aminoglycosides.

The bioavailability of paromomycin when administered as a single oral dose of 150 mg paromomycin/kg bodyweight to 8 - 10 days old calves was 3.23 %. With regard to the absorbed fraction, the mean peak plasma concentration (Cmax) was 4.148 ± 3.106 mg/l, the median time to attain the peak plasma concentration (Tmax) was 4.75 hours (2-12 h) and the mean terminal half-life (t1/2) was about 10 hours. The main part of the dose is eliminated unchanged in the faeces while the absorbed fraction is excreted almost exclusively in urine as unchanged paromomycin. Paromomycin displays age-related pharmacokinetics, with the greatest systemic exposure occurring in newborn animals.

The active ingredient paromomycin sulfate binds strongly to soil and is very persistent in the environment