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Pharmacokinetics of minocycline and vancomycin in rabbits.

The pharmacokinetic disposition of minocycline and vancomycin was studied in New Zealand White rabbits before initiating an experimental staphylococcal endocarditis protocol. Minocycline was administered in a multiple-dose regimen of 3 mg/kg i.v. every 12 h, 3 mg/kg i.v. every 8 h, and 6 mg/kg i.v. every 8 h. Vancomycin was given in a similar fashion using regimens of 75 mg/kg i.v. every 12 h and 50 mg/kg i.v. every 8 h. Multiple serum samples were obtained after the fifth dose and drug concentrations were analyzed by microbiologic assay. The pharmacokinetic parameters for each of the drug regimens were calculated using a two-compartment model by nonlinear least-squares regression. No statistically significant differences were noted in the volume of distribution or the half-life of the individual dosing regimens for either agent. As a result of this study, it appears that a minocycline regimen of 6 mg/kg i.v. every 8 h and a vancomycin regimen of 50 mg/kg i.v. every 8 h are appropriate dosing schemes for a comparative study of these agents in rabbits.