Pharmacology: Pharmacodynamics: Mechanism of Action:
Bacteriology: Spectrum: This product exhibits in vitro and in experimental animals in vivo, bactericidal activity against a wide range of Gram-positive and Gram-negative bacteria. The following are among the more commonly encountered sensitive organisms: (See Table 1.)
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Synergism: It exhibits synergistic bactericidal activity in vitro, and in experimental animals in vivo against some ampicillin-resistant organisms.
Additive effects: The two components of this product-amoxicillin and flucloxacillin - generally exhibit an additive effect against sensitive bacteria and bacteria that are sensitive to amoxicillin or to flucloxacillin remain sensitive to the combination, showing that antagonism does not occur when the two components are combined.
It is well absorbed orally. Peak serum levels are achieved 1 to 2 hours after dosing.
Absorption is more efficient when taken on empty stomach. The total quantity absorbed by the oral route represents approximately 79% of the quantity administered.
Amoxicillin diffuses readily into most body tissues and fluids, with the exception of brain and spinal fluid, except when meninges are inflamed. Most of the amoxicillin is excreted unchanged in the urine.
Its excretion can be delayed by concurrent administration of probenecid. Flucloxacillin diffuses well into most tissues specifically, active concentration of flucloxacillin have been recovered in bones: 11.6 mg/l (Compact bone) and 156 mg/l (spongy bone), with a mean serum level of 8.9 mg/l. Crossing the meningeal barrier: flucloxacillin diffuses in only small proportion into cerebrospina1 fluid of subjects whose meninges are not inflamed.
Approximately 50% of the dose is excreted unchanged into the urine within 6 hours, resulting in high urine levels of active drug.
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.
The serum protein binding rate is 95% in case of flucloxacillin whereas 20% of amoxicillin is protein bound.