Adam D, Bauer W, Seitz B, Voigt I
Arzneimittelforschung. 1979;29(11):1769-804.
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.
对正常志愿者静脉注射不同剂量的广谱青霉素(氨苄西林、美洛西林、羧苄西林),单独使用或与苯唑西林同时联合使用,评估血清水平变化过程和尿液中的回收情况,并针对一室模型计算药代动力学数据,某些情况下也针对二室模型进行计算。对以下青霉素进行了单独测试以及与苯唑西林联合测试:氨苄西林3g、苯唑西林2g及其组合;氨苄西林2g、苯唑西林1g及其组合;美洛西林3.75g、苯唑西林1.25g及其组合;美洛西林2g、苯唑西林1g及其组合;羧苄西林7.5g、苯唑西林2.5g及其组合。除一种组合(苯唑西林2g + 氨苄西林3g)外,所有青霉素组合在任何时间的血清水平均超过单独给药后的水平。在组合用药时,消除常数降低,总清除率降低,半衰期延长。分布容积各不相同。除了一个例外,即苯唑西林2.5g + 羧苄西林7.5g,所有组合的尿液回收量均高于单独给药。静脉同时注射两种青霉素时,必须考虑到一个类似于丙磺舒与卡隆酰胺联合给药后的过程。可以假定联合给药后血清水平的延长和升高同样会导致更高的组织浓度,这种效应可能具有临床意义。