Amoxicillin for chest infection

Prosthetic devices are particularly susceptible to infections, more than 50% of which are due to Staphylococcus aureus or coagulase-negative staphylococci, such as S. It is vitally important that adequate surgical prophylaxis be used and that

sufficient

Successful treatment of

infections

For the timing of perioperative prophylaxis and surgery, it seems critical to

know

Modeling of the time course of bone concentrations for penicillins is important, since the shape of the concentration-time curve affects the time above the MIC. The concentrations of amoxicillin and clavulanic acid in bone were studied in the 1980s (1, 3, 24, 54), and only the bone concentration/serum concentration ratios were reported. As these bone concentration/serum concentration ratios change over time, they are a suboptimal measure of the extent of tissue penetration (36, 47).

For patients undergoing joint replacement surgery, only one bone sample is most commonly available per patient. Population pharmacokinetic (PK) modeling offers the advantage that it can fit the full time course of the bone and serum concentrations on the basis of the data for all patients simultaneously. The extent of bone penetration is best described by the ratio of

the

The second objective was to develop a PK model which describes the time course of the amoxicillin and clavulanic acid concentrations in bone as well as the drug exposure in bone relative to that in serum. The third objective was to evaluate the PD profile of amoxicillin in serum, cortical, and cancellous bone (16, 19) against pathogens commonly encountered in bone infections, such as MSSA and S.

Twenty patients (9 males, 11 females) who were scheduled to undergo total hip replacement participated in this controlled clinical study. The patients were diagnosed with coxarthosis and had no inflammation of the joints.

Their average

weight

The study was approved by the Institutional Review Board of the School of Medicine, Friedrich-Alexander-University Erlangen-Nurnberg, and was performed according to the revised version of the Declaration of Helsinki.

All subjects gave their written informed consent prior to entry into the study. A single dose of 2,000 mg amoxicillin in combination with 200 mg clavulanic acid (

Augmentin

In addition, each patient received a single oral dose of moxifloxacin 2 to 7 h before surgery.

Blood samples were collected predosing and at the time of femoral bone resection. The samples were placed in an ice-water bath and were left to clot before they were centrifuged at 4°C. After centrifugation, the serum samples were amoxicillin petsmart immediately frozen

and

ice

The adhering blood was removed from the samples by swabbing for a short time.

The bone samples were subsequently pulverized under liquid nitrogen by use of a cryogenic mill (Freezer/Mill).

For preparation of calibration standards and spiked quality controls, appropriate amounts of amoxicillin and clavulanic acid standard solutions were added to serum and bone tissue samples that were shown to be free of the study drugs.

For determination of the amoxicillin and clavulanic acid concentrations in serum, 50 ?l of the internal

standard

The samples were deproteinized by addition of 300 ?l acetonitrile.

After the samples were thoroughly mixed, they were centrifuged and 50 ?l of the clear supernatant was analyzed amoxicillin 500 uses by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

For analysis of the bone samples, an aliquot of the bone powder was shaken with six times the amount of buffer for 4 h.

The degree of extraction was studied over time to ensure the reproducibility of the results.

Amoxicillin and clavulanic acid were stable during the 4-h extraction period.

After centrifugation, 50 ?l of the internal standard solution was added to 50 ?l of the aqueous supernatant. After addition of 175 ?l acetonitrile, the samples were thoroughly mixed and centrifuged. The clear supernatant was diluted with twice the amount of buffer. For determination of the amoxicillin concentration, 50 ?l of each sample was chromatographed on a reversed-phase column (Ultracarb 5 ODS 30) and eluted by use of an isocratic solvent system consisting of 0.001 M ammonium acetate buffer and acetonitrile (90/10, vol/vol). The samples were monitored by LC-MS/MS by the selected reaction monitoring method: precursor > product ion for amoxicillin, m/z 366 > m/z 208; precursor > product ion for the internal standard, m/z 350 > m/z 160. Under these conditions, amoxicillin and the internal standard were eluted after approximately 0.8 min.

For determination of the clavulanic acid concentration, 25 ?l of each sample was chromatographed on a reversed-phase column (Nucleosil 100 amino) and eluted by use of an isocratic solvent system consisting of 0.01 M

ammonium

Under these conditions, clavulanic acid and the internal standard were eluted after approximately 2 min.

MacQuan software (version 1.4-noFPU; Perkin-Elmer, Toronto, Ontario, Canada) was used for evaluation of the chromatograms.

No interference was observed for the study drugs or the internal

standards

The precision and the accuracy of the spiked quality controls for amoxicillin in serum ranged from 1.8 to 10% and 97.3 to 107.8%, respectively, and the precision and the accuracy of the spiked quality controls for clavulanic acid in serum ranged from 0.8 to 4.8% and 96.0 to 100.5%, respectively.

The precision and the accuracy of the spiked quality controls for amoxicillin in bone homogenate ranged from 5.8 to 8.1% and 97.2 to 99.5%, respectively.

The

for

A bone compartment was added to model the concentrations in bone.

The drug input into the central compartment was described by a time-constrained zero-order process.

Standard diagnostic plots for model evaluation were used, and the predictive performance of the final model was tested by the use of visual predictive checks.

For the visual predictive check, serum and bone concentration curves for 10,000 subjects were simulated for amoxicillin and clavulanic acid. We derived the median, the nonparametric 90% prediction interval (

5th

We compared the median predicted concentrations and the prediction intervals with the observed data and performed a visual assessment to determine whether the median and the predicted intervals adequately mirrored the central tendency and the variability of the observed data. Observations for amoxicillin and clavulanic acid concentrations in serum, cortical bone, and cancellous bone were available.

The differential equations for amoxicillin were as follows: $$mathtex$$\[\frac \mathrm \ \left(\frac \mathrm \mathrm _ >> >>\right)\ \ X1 \frac > >>\ \ X2 \frac _ >> >>\ \ X3\]$$mathtex$$ $$mathtex$$\[\frac \frac > >>\ \ X1 \frac > >>\ \ X2\]$$mathtex$$ $$mathtex$$\[\frac \frac _ >> >>\ \ X1 \frac _ >> >>\ \ X3\]$$mathtex$$ where compartment 1 is the central compartment, compartment 2 is the peripheral compartment, and compartment 3 is the bone compartment; X 1, X 2, and X 3 represent the amounts of drug in the central, peripheral, and bone compartments; V c entral , V p eripheral , and V b one represent the volumes of distribution in the central, peripheral, and bone compartments. Initial conditions were 0 for all three compartments. CL is the total clearance from the central compartment, CLic is the intercompartmental clearance between the central and the peripheral compartments, and CLic bone is the intercompartmental clearance between the central and the bone compartments. The differential equations for clavulanic acid can be obtained from the above equations by setting CLic equal to 0.

The observed bone concentrations and initial modeling showed that the rates of equilibration between serum and cortical bone as well as those between serum and cancellous bone were similar.