[Pharmacokinetic studies on broad spectrum antibiotic combinations of penicillin and oxacillin in normal volunteers (author's transl)]

Abstract

After i.v. application of broad spectrum penicillins (ampicillin, mezlocillin, carbenicillin) alone or combined with oxacillin (concomitantly) in different dosages to normal volunteers, the course of serum levels and recovery from urine were assessed and pharmacokinetic data were calculated for a 1-compartment model, in some cases also for a 2-compartment model. The following penicillins were tested alone and combined with oxacillin; ampicillin 3 g, oxacillin 2 g and their combination; ampicillin 2 g, oxacillin 1 g and their combination; mezlocillin 3.75 g, oxacillin 1.25 g and their combination; mezlocillin 2 g, oxacillin 1 g and their combination; carbenicillin 7.5 g, oxacillin 2.5 g and their combination. Apart from one combination (oxacillin 2 g + ampicillin 3 g), all penicillin combinations exceeded the serum levels achieved after individual application at any time. In combinations, the elimination constants decreased, total clearance was lower, and half-lives increased. The distribution volumes varied. With one exception, oxacillin 2.5 g + carbenicillin 7.5 g, all the combinations yielded a higher recovery from urine than did individual administration. When administering i.v. two penicillins simultaneously, a process similar to that following administration of probenecid in association with caronamide must need be considered. It may be assumed that the prolongation and elevation of serum levels after combined administration likewise lead to higher tissue concentrations, which effect might be of clinical consequence.