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The serum protein binding, extravascular diffusion and urinary excretion of teicoplanin were studied in rabbits. Extravascular diffusion was studied after a 20 min iv infusion, and after one or five im injections (7·5 mg/kg), and was compared with the results obtained after im administration of vancomycin (7·5 and 15 mg/kg). In an experimental model of endocarditis, the efficacy of both antibiotics was also investigated. We observed teicoplanin serum protein binding of 87±4%. The serum concentrations of teicoplanin showed a three-phase exponential decline: T 0·11 ±0·01 h; T, l·4±0·4 h; T, 8·3±2·2 h. Teicoplanin appeared to be slightly secreted by renal tubules. The extravascular diffusion and the therapeutic efficacy of both drugs were studied with intervals between two injections based on the same multiple of β half-life. Teicoplanin, like vancomydn, appeared slowly in extravascular fluid and the diffusibility of both drugs was similar. Peak extravascular concentrations of teicoplanin after 5 im injections were greater when the compound was administered every 16 h, rather than every 24 h and, for this drug, iv administration induced higher peak extravascular concentrations (P > 0·01) than im injection. In the experimental model of S. aureus endocarditis, vancomycin 9 mg/kg/12 h and teicoplanin 4·5 mg/kg/16 h were similarly active and more effective than teicoplanin 4·5 mg/kg/24 h. [ABSTRACT FROM PUBLISHER]

The pharmacokinetics of gentamicin and latamoxef (moxalactam) were examined in serum, normal heart valves, sterile cardiac vegetations and vegetations infected with . Penetration of antibiotics into heart valves and vegetations was rapid; the maximum concentration was achieved in both sites at the end of a 20 min iv infusion. However, both antibiotics penetrated better into vegetations than into normal heart valves. In rabbits with left-sided endocarditis, similar antibiotic levels were found in infected vegetations after one or 22 im injections. After 11 im injections (one every 8 h) of latamoxef (15 mg/kg) the bacterial titre (cfu/g) was significantly reduced, but not nil, despite concentrations about 40 times the MBC for this antibiotic in the vegetations. Afer 22 im injections, vegetations in rabbits receiving latamoxef were sterile and were significantly reduced in those receiving gentamicin (1.5 mg/kg/im), concentrations of which in the vegetations were inferior to the MBC. Our results suggest that the antibacterial effect depends on local antibiotic levels, kinetics of killing and duration of contact between antibiotic and bacteria. [ABSTRACT FROM PUBLISHER]

The serum protein binding, extravascular diffusion and urinary excretion of pefloxacin were studied in rabbits. The effect of furosemide on the urinary excretion of pefloxacin was investigated. In an experimental model of Escherichia coli endocarditis, diffusion into heart valves and infected vegetations and bactericidal effect of pefloxacin were also studied. We observed a serum protein binding of 25%. Extravascular concentrations found were within the range of the minimal inhibitory concentrations for most susceptible strains. Pefloxacin appeared to be reabsorbed by renal tubules (fractional excretion: 61 +/- 21%). Furosemide significantly increased the renal excretion of pefloxacin through a tubular process. We observed a good penetration of pefloxacin into normal heart valves and infected vegetations. Pefloxacin reduced the colony counts in infected vegetations after seven im injections of the drug (given as 15 mg/kg/12 h). [ABSTRACT FROM AUTHOR]