title: Comparative distribution of gentamicin, tobramycin, sisomicin, netilmicin, and amikacin in interstitial fluid in rabbits.
abstract: We compared the penetration of five aminoglycosides into interstitial fluid (IF). IF was obtained in rabbits from Silastic tissue cages. Intramuscular injections were made: 1.5 mg/kg per dose for gentamicin (G), tobramycin (T), sisomicin (S), and netilmicin (N) and 7.5 mg/kg per dose for amikacin (A). Serum levels and IF concentrations were studied for 12 h after a single injection. IF levels were also compared in a six-injection study (one injection every 8 h). Peak serum levels were significantly higher with A than with G, T, S, and N, which gave similar concentrations. In IF, G gave the highest levels 1 h after the first injection. At 4 and 8 h, the concentrations achieved with G and A were similar but significantly greater than those achieved with T, S, and N. Twelve hours after a single injection, N gave higher IF levels than the other drugs except A. In the six-injection study, the IF levels of G and A reached 4.6 +/- 1.5 and 5.27 +/- 1.1 microgram/ml, respectively, at 48 h. S and N gave identical concentrations (2.07 +/- 0.25 and 2.42 +/- 0.42 microgram/ml, respectively). T induced the lowest levels (1.17 +/- 0.30 microgram/ml). Thus, in this rabbit model, the IF concentrations achieved with G and A were above the minimal inhibitory concentrations for most susceptible strains. Possible relations between IF aminoglycoside concentrations and therapeutic efficiency or toxicity are pointed out but deserve further studies.
mesh_terms: D000583:Amikacin / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D005110:Extracellular Space / Q000032:analysis / Q000378:metabolism*; D005260:Female; D005839:Gentamicins / Q000032:analysis / Q000378:metabolism*; D007273:Injections, Intramuscular; D007700:Kinetics; D009428:Netilmicin / Q000032:analysis / Q000378:metabolism*; D011817:Rabbits; D012853:Sisomicin / Q000032:analysis / Q000378:metabolism*; D014031:Tobramycin / Q000032:analysis / Q000378:metabolism*
chemical_list: D005839:Gentamicins; D009428:Netilmicin; D000583:Amikacin; D014031:Tobramycin; D012853:Sisomicin
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