Pharmacokinetics of amoxicillin and flucloxacillin following the simultaneous intravenous administration of 4 g and 1 g, respectively

Abstract

The combination of amoxicillin and flucloxacillin not only widens the spectrum of pathogenic organisms covered by either of the substances alone; synergy has also been observed, particularly against beta-lactamase-producing organisms. For this reason, the possible interaction of these two penicillins regarding their pharmacokinetics was investigated with respect to therapeutic application. The parameters were calculated on the basis of an open two-compartment model. The highest serum levels of amoxicillin from 551 to 1074 mg/l when 4 g were administered alone, and from 403 to 1133 mg/l when administered together with 1 g flucloxacillin. Flucloxacillin concentrations ranged from 118 to 357 mg/l when administered alone, and from 151 to 226 mg/l in the presence of amoxicillin. Thus, there is no significant difference in the peak levels of either substance when given alone or in combination. The pharmacokinetic parameters of both substances basically do not depend on the presence of the other. A slight decrease was observed in the distribution rate of amoxicillin from the central to the peripheral compartment in the presence of flucloxacillin. Its relevance is questionable, however, since the effect was only minor.

Penicillinase-resistant antibiotics induce non-immune-mediated cholestasis through HSP27 activation associated with PKC/P38 and PI3K/AKT signaling pathways

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