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Amoxicillin 500 mg tablet
When calculated in relation to total bone, the average amoxicillin concentrations were about 8 mg/kg of bone and the average clavulanic acid concentrations were 0.7 to 0.8 mg/kg at up to 2 h after administration of the dose, and the average amoxicillin concentrations were about 2.5 mg/kg of bone and the average clavulanic acid concentrations were about 0.3 mg/kg 2 to 4 h after administration of the dose. This corresponds to average ratios for total bone concentration/serum concentration of approximately 8 to 14% and 4 to 8% for amoxicillin and clavulanic acid during the first 2 h and 15 to 18% and 6 to 7% for amoxicillin and clavulanic acid at 2 to 4 h (54). (3) studied amoxicillin bone penetration in 26 patients on average 2 h (range, 1 to 2.5 h) after the administration of a single oral dose of 500 mg. The average bone concentration-to-serum concentration ratios were 16% (range, 3.7% lupus and amoxicillin to 28%) for mandibular bone and 26% (range, 5.6% to 55%) for maxillary bone, which were similar to the findings of our study. (50) reported an average bone concentration/serum concentration ratio of 8.2% in the jaw bones of nine patients who were receiving 500 mg amoxicillin every 8 h for 2 days and to whom the last dose was given at about 2 h before surgery. (1) found 9.8 mg/kg clavulanic-acid in cancellous bone and 15 mg/kg in cortical bone at 0.5 to 1 h after the end of a 20-min infusion of 200 mg clavulanic acid. The bone amoxicillin-clavulanic acid concentrations from Grimer et al. (54) were approximately 2 to 3 times lower than those from our study, whereas Adam et al. (1) reported clavulanic acid concentrations about 10 times higher than those obtained in our study (Fig. This pronounced difference (20- to 30-fold for averages) for clavulanic acid calls for standardized methods of sample preparation, drug analysis, and PK evaluation. The concentrations of amoxicillin and clavulanic acid showed a high correlation in cortical bone ( r = 0.90; observed data) and cancellous bone ( r = 0.95; Fig. This suggests that both drugs were stable and that sample preparation and drug analysis were precise and reproducible. The concentrations in cortical and cancellous bone were correlated for both drugs ( r = 0.75). (54) and indicates that the equilibration rates between cortical bone and serum and between cancellous bone and serum were probably similar. Consequently, the equilibration half-lives for both types of bone were assumed to be the same in the final model. Short equilibration half-lives between bone and serum were estimated for both drugs (Table 1; Fig. This suggests that concentrations above the PK-PD breakpoints were reached within less than 30 min after the end of a 30-min infusion. As serum and bone concentrations are decreasing after the end of a short-term infusion, these fast equilibration half-lives suggest from a PK point of view that the surgery should start within the first 30 min after the end of a 30-min infusion. As the breakpoints reported here are based on PK-PD targets for the doxycycline and amoxicillin together treatment of infections and as these targets were derived on the basis of the plasma or serum concentrations, PK-PD targets for surgical prophylaxis need to be established and our simulation results should be interpreted conservatively. The determination of total antibiotic concentrations in bone homogenate, as reported in virtually all studies on bone penetration published to date (36), has several limitations. Bone tissue consists of an organic matrix (30 to 35% of total bone mass) and an inorganic matrix (65 to 70%) (14, 25, 48). The organic matrix mainly consists of collagen fibrils, glycoproteins, proteoglycans, kimoxil amoxicillin extracellular fluid (25), and bone cells (1 to 2% of the total bone mass) (14). The inorganic matrix is formed by hydroxyapatite crystals (calcium phosphate) deposited within the organic matrix (14). Neither antibiotics nor bacteria are expected to distribute homogeneously in bone. No techniques for the separation of bone samples into extracellular fluid, hydroxyapatite, collagen fibrils, and bone cells are currently available. In addition, only the unbound fraction of drug is considered to be microbiologically active, and the extent of binding in bone is not known. Binding experiments suggest that beta-lactams do not bind (or bind only to a minor extent) to bone powder or hydroxyapatite crystals (1, 55). Beta-lactams likely distribute mainly within the vascular and extracellular fluid spaces in bone (17, 26, 34, 41). They pass the capillary walls of blood vessels located amoxicillin 500 buy in the Haversian and Volkmann canals in bone, diffuse into the interstitial fluid space, and likely distribute in the lacunocanalicular system (Table 4, scenarios B and C) (15, 34). Furthermore, bacteria are not expected to distribute into the inorganic matrix or collagen fibrils but mainly distribute in the interstitial and extracellular fluid spaces (scenarios B and C). Therefore, scenarios B and C in Table 4 seem to be the most likely, and the breakpoints reported in Table 2 appear to be conservative (i.e., low) estimates, if the bacteria do not distribute intracellularly and do not reside in sequestered areas. As it is not known how drug and bacteria distribute within bone, Table 4 lists potential breakpoints for a dose of 2,000/200 mg amoxicillin-clavulanic acid q6h for various distribution scenarios.
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