The pharmacokinetics and extravascular diffusion of teicoplanin in rabbits and comparative efficacy with vancomycin...

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 Staphylococcus aureus 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: T1/2 alpha, 0.11 +/- 0.01 h; T1/2 beta, 1.4 +/- 0.4 h; T1/2 gamma, 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 beta half-life. Teicoplanin, like vancomycin, 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 less than 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.