Neomycin Sulfate: Overview, Pharmacokinetics and Mechanism of Action

General Description

Neomycin sulfate, a broad-spectrum aminoglycoside antibiotic, comprises neomycin B and C, inhibiting bacterial protein synthesis. It is used in various pharmaceutical preparations for bacterial infections in different medical fields. It is a water-soluble complex of aminoglycoside antibiotics. It may be administrated by ophthalmic, topical, oral (p.o.), and intravenous (i.v.) administrations. The European Medicines Evaluation Agency (EMA, 2002) indicated that neomycin is poorly absorbed in the gastrointestinal tracts of humans and animals.¹

Figure 1. Neomycin Sulfate

Pharmacokinetics

Neomycin sulfate is an aminoglycoside antibiotic used in veterinary medicine, exhibits distinct pharmacokinetic properties in swine following intravenous (i.v.) and oral (p.o.) administrations. In swine, oral administration results in an elimination half-life of 12.43 ± 7.63 hours, with a mean maximum concentration of 0.11 ± 0.07 μg/ml and a mean time to reach maximum concentration of 1.92 ± 0.97 hours. The area under the concentration-time curve from t0 to the last collection point is 1.23 ± 0.78 μg·h/ml. In contrast, after i.v. administration, the elimination half-life is shorter at 5.87 ± 1.12 hours, with a substantially higher mean maximum concentration of 15.80 ± 1.32 μg/ml, and a shorter mean time to reach maximum concentration of 0.30 ± 0.38 hours. The area under the concentration-time curve from t0 to the last collection point is markedly higher at 76.14 ± 3.52 μg·h/ml. The absolute bioavailability of neomycin sulfate B is low, measured at 4.84%±0.03. Additionally, neomycin sulfate exhibits poor gastrointestinal absorption, with increased absorption in the presence of inflammatory or ulcerative gastrointestinal disease. It is rapidly distributed in tissues and has a low protein binding profile, ranging from 0-30%. Metabolism is deemed negligible, with the small fraction of absorbed neomycin primarily excreted unchanged by the kidneys, while the unabsorbed portion is eliminated in the feces. Limited information is available on its half-life and clearance rate. 

In conclusion, the pharmacokinetic characteristics were a long T1/2 and a slow clearance rate. The absolute bioavailability of neomycin sulfate in after oral administration is low, and subsequent studies can improve the absolute bioavailability to treat systemic infections by changing the dosage form or adjuvant.¹

Mechanism of Action

Neomycin sulfate exerts its pharmacological effects primarily by inhibiting bacterial protein synthesis, which ultimately leads to the suppression of bacterial growth and survival. Neomycin sulfate is effective against both gram-positive and gram-negative organisms, including major E. coli species found in the colon and enteropathogenic forms of E. coli, as well as the Klebsiella-Enterobacter group. When administered orally, Neomycin sulfate's bactericidal activity can last from 48 to 72 hours. In addition to its direct antibacterial effects, neomycin has been used as an adjunctive therapy in hepatic coma to improve neurological symptoms by reducing colonic bacteria that produce ammonia.  Neomycin sulfate achieves its bactericidal action by binding to the 30S ribosomal subunit of susceptible bacteria, which disrupts the translational machinery of bacterial protein synthesis. This prevents the normal initiation of bacterial translation, where mRNA binds to the 30S subunit and subsequently with the 50S subunit for elongation.  It's worth noting that while neomycin has no antifungal activity, it does exhibit some activity against certain protozoa. However, prolonged use of Neomycin sulfate can lead to the emergence of resistant strains of bacteria, such as E. coli, Klebsiella, and Proteus spp.²

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