SERUM AND MILK CONCENTRATIONS OF APRAMYCIN IN LACTATING COWS, EWES AND GOATS
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
Authors: ZIV, G; KURTZ, B; RISENBERG, R; GLICKMAN, A
A 20% solution of apramycin was administered intravenously (i.v.) and intramuscularly (i,m,) to lactating cows with clinically normal and acutely inflamed udders, to lactating ewes with normal or subclinically infected, inflamed udders and i,v. to lactating goats with normal udders, The i,v, disposition kinetics of apramycin was very similar in cows, ewes and goats. The elimination half-life was approximately 2 h and the steady-state volume of distribution was 1.26-1.45 L/kg, The absorption rate of the drug from the i,m, injection site was rapid, the i,m. bioavailability was 60-70% and the mean elimination half-life was 265 min in cows and 145.5 min in ewes. The binding percentage of apramycin to serum protein was low (< 22.5%), Concentrations of apramycin in milk produced by clinically normal mammary glands of cows, ewes and goats were consistently lower than in serum; the kinetic value AUC(milk)/AUC(serum) was < 0.32, Drug penetration into the milk from the acutely inflamed quarters of cows was extensive; mastitis milk C-max values were more than tenfold greater than the C-max in normal milk, On the other hand, the drug had limited access to the milk produced by subclinically infected inflamed half-udders of ewes.
Evaluation of apramycin against spectinomycin-resistant and -susceptible strains of Neisseria gonorrhoeae
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Authors: Riedel, Stefan; Vijayakumar, Divya; Berg, Gretchen; Kang, Anthony D.; Smith, Kenneth P.; Kirby, James E.
Background: The emergence of Neisseria gonorrhoeae resistant to all currently available antimicrobial therapies poses a dire public health threat. New antimicrobial agents with activity against N. gonorrhoeae are urgently needed. Apramycin is an aminocyclitol aminoglycoside with broad-spectrumin vitro activity against MDR Gram-negative pathogens and Staphylococcus aureus. However, its activity against N. gonorrhoeae has not been described. Objectives: The activity spectrum of apramycin against a collection of MDR N. gonorrhoeae was assessed. Isolates tested included those susceptible and resistant to the structurally distinct aminocyclitol, spectinomycin. Results: The modal MICs for apramycin and spectinomycin were 16 mg/L and 32mg/L, respectively. The epidemiological cut-off (ECOFF) for apramycin was 64 mg/L. No strains among 77 tested had an MIC above this ECOFF, suggesting very low levels of acquired apramycin resistance. In time-kill analysis, apramycin demonstrated rapid bactericidal activity comparable to that of spectinomycin. Conclusions: Apramycin has broad-spectrum, rapidly bactericidal activity against N. gonorrhoeae. Future pharmacokinetic and pharmacodynamic studies will be needed to determine whether apramycin and/or apramycin derivatives hold promise as new therapeutics for N. gonorrhoeae infection.