Amoxicillin and metformin

Precision and accuracy data were obtained by analyzing aliquots of three spiked plasma at low (3 m g/ml) middle (25 m g/ml) and high (50 m g/ml) concentration levels of AMO. Intra-day reproducibility was determined by analyzing 5 aliquots of spiked human plasma and inter-day reproducibility was determined over a 5-day period (n=5). The following test formulation was employed: 500mg Amoxicilina capsules from Brazil (AC 309/Production date 03/2000; Expiry date 03/2002). The details of the reference formulation are as follows: 500mg Amoxil® capsules produced by SmithKline Beecham (BB0028/Production date 01/2000; Expiry date 01/2002). Twenty-four (12 male and 12 female) adult volunteers, non-smokers, aged between enterococcus faecalis amoxicillin 21 and 47 years, weighing between 55 and 95 kg and within 15% of the ideal body weight, were selected for the study.

The volunteers were not on concomitant medications and were free from significant cardiac, hepatic, renal, pulmonary, gastrointestinal, neurological or hematological disease as determined within four weeks prior to the beginning of the study by way of medical histories, physical examinations and the following laboratory screenings: fasting blood glucose, urea, creatinine, SGOT (AST), SGPT (ALT), total bilirubin, total protein, plasma albumin, alkaline phosphatasis, sodium, potassium, chloride, uric acid, urinalysis, hemoglobin, hematocrit and total differential white blood cells count.

All volunteers gave written informed consent and the Ethics Committee of Sao Francisco University Hospital approved

the

After administration of the capsule, the volunteers were asked to drink 200ml of tap water.

Blood samples for plasma drug assay were taken from a forearm vein at 0, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hours after AMO administration.

On each occasion, one 5ml sample was taken via "butterfly" into a clean tube. After blood clotting at room temperature, the blood samples were centrifuged at 2000g for ten minutes and the plasma removed and stored at -70°C until assayed.

The volunteers received 200ml of tap water drink three hours after dose administration.

Six hours after dose administration a standard lunch was made available and an evening meal was provided twelve hours after administration of the dose.

Liquids were allowed ad libitum after lunch, but xanthine-containing beverages, such as tea, coffee and cola were not permitted. Maximum observed plasma concentration (C max ) and time taken to reach it (T max ) were obtained from drug concentration vs.

time curves from 0-8 hours (AUC 0-8h ) were calculated using the trapezoidal method and the first order elimination rate

constant

C max and AUC 0-8h data were analyzed statistically using both parametric (one-way ANOVA) and non-parametric methods (Wilcoxon's signed ranks test). The alternative HPLC-UV method described and used here for drug quantification provides the appropriated sensitivity, specificity and high sample throughput required for pharmacokinetic studies. Figure 2 shows that under described chromatographic conditions, the retention times for AMO and internal standard were 4.2 and 5.2min, respectively.

As also shown in Figure 2, no endogenous interfering peaks appeared at the retention times of the compounds of interest. Figure 2: Chromatographic analysis of amoxicillin A) plasma blank; B) plasma + internal standard (cefadroxil 15 m g/ml); C) plasma + amoxicillin (20 m g/ml) + internal standard (cefadroxil 15 m g/ml); D) Chromatogram obtained from plasma of a volunteer following oral administration of Amoxicillin (500mg).

The mean absolute recovery of AMO in plasma was 90.0% at 3?g/ml, 98.6% at 25 m g/ml and 95.3 at 50 m g/ml.

The LOD and the LOQ for AMO were 0.1 and 1g/ml, respectively. The calibration curve was linear over the range 1.0g/ml to 50g/ml, with a regression coefficient ? 0.999 and intercept not significantly different from zero (Figure 3). The analytical precision and accuracy obtained for intra-day and inter-day assays of four quality controls (1, 3, 25 and 50 m g/ml; n=5) are shown in Table 1. Table 1: Analytical precision and accuracy of the determination of amoxicillin from spiked plasma samples (n=5).

The overall variability (n=48) was 11.0, 6.5, 5.2 and 4.8% respectively; and the accuracy was 102.8, 103.3, 103.0, 106.8%. No significant degradation of AMO was observed during this period under the storage conditions. AMO was well tolerated at the administered dose, and no adverse effects were reported.

Figure 4 shows mean AMO plasma concentrations as a function of time after the oral administration of 500mg AMO of both brands. The major mean pharmacokinetic parameters derived from the plasma concentration vs. The geometric mean ratios for AUC0-8h and Cmax of the two AMO oral formulations are shown in Table 3, along with analyses of their position in relation to the 80-125% interval using different tests.

Figure 4: Curves of the mean plasma concentration of amoxicillin (± SEM) of 24 volunteers vs. Table 2: Mean pharmacokinetic parameters obtained in 24 healthy volunteers after the administration of both 500mg amoxicillin formulations.

Table 3: Statistical analysis of AUC 0-8h and C max ratios between Amoxicilina (Test) and Amoxil® (Standard). AMO plasma levels have been measured by other methods using HPLC in combination with UV detection (14-19).

The lowest limit of quantification obtained by UV detection was 50ng/ml, but the elution times for both AMO and internal standard were 31.8 and 32.8 min, respectively, much longer amoxicillin clavulanic acid 1000 mg than those reported herein (14). The method of Chulavatnatol & Charles was described only for the measurement of amoxicillin in urine (19). A simple high-performance liquid chromatographic method involving protein precipitation and ultraviolet detection at 220 nm was reported by Hoizey et al. for the simultaneous determination of AMO and clavulanic acid in human plasma (15).

Unfortunately, the LOQ obtained for AMO was 635 m g/ml, even higher than in our method (1 m g/ml). Other more complicated extraction procedures such as solid-phase extraction have also been reported (17, 18, 24-26). Nevertheless, solid-phase extraction procedures are laborious and require SPE cartridges, increasing the cost of the analysis.

In order to improve sensitivity, a column switching ion-pair reversed phase liquid chromatographic system with a post column derivatization method has been used by Carlqvist & Westerlund (23).

However, their assay, where the limit of quantification was 10ng/ml, has been carried out with no internal standard.

In addition the method was complex due to the post column derivatization step.

Their retention time was also longer for the analyte (approximately 10 min as compared to our 4 min) and additionally was not used for a pharmacokinetic study in humans where a large number of samples were analyzed. Derivatization of AMO to a fluorescent compound showed similar sensitivity and slightly longer retention time (4.5 min for AMO), but does involve a complex chromatography system including electrochemical detection (20).

and Mascher & Kikuta have satisfactory limits of quantification but do not utilize an internal standard, which is required for an HPLC method meeting GLP guidelines (20, 22).

reported the determination of AMO using LC-MS-MS detection. Mass spectrometers, however, are expensive and not readily available.

Furthermore, the solid-phase extraction procedure employed need laborious sample pre-treatment and requires SPE cartridges, increasing the cost of the analysis (26).

The method presented here is less sensitive than many other available assays, i.e., 1 m g/ml.

However, this level of sensitivity was sufficient to perform the bioequivalence study.

The pharmacokinetic study was done in 8 hours and the resulting value of AUC 0- Ґ? was less than 20% higher than that of AUC 0-8 for both formulations (12 and 13.9% for Amoxicilina and Amoxil respectively), as recommended by the regulatory agency. Later samples (12 and 24h after the administration of the drug) were taken and analyzed, but no better estimation of AUC 0- Ґ? was observed and the differences between the values remain virtually the same. The choice of Cefadroxil as an internal standard for AMO was based on the presence of similar functional groups in both structures in addition to their similarity in terms of elemental compositions and chemical behavior. Several wavelengths (225-330nm) were evaluated and 229 nm produced the best results in terms of selectivity and sensitivity. Considering the fact that the present method involves a shorter running time and a simple sample preparation process, it may be used in similar studies as a time and cost effective alternative to other available methods. The validated HPLC method employed here proved to be simple, fast, reliable, selective and sensitive enough to be used in clinical pharmacokinetic studies of AMO in humans.

The median T max and C max values for both oral formulations were similar to those reported in the literature. The present study shows that Amoxicilina 500mg capsules was bioequivalent to Amoxil® capsules 500mg, in terms of both the rate and extent of absorption, as assessed by the appearance of 90% CI for both AUC 0-8h and C max ratios within the 80-125% interval proposed by the Food and Drug Administration . Tomas, A., From penicillin-binding proteins to the lysis and death of bacteria. Tomas, A., The mechanism of irreversible antimicrobial effect of penicillins: how the beta lactam antibiotics kill and lyse bacteria.

L., Interaction of penicillin with the bacterial cell: penicillin-binding proteins and penicillin-sensitive enzymes.

L., Penicillin-binding proteins and the mechanisms of action of beta-lactam antibiotics. N., Amino-p-hydroxybenzil penicillin (BRL 2333), a new semi synthetic penicillin: in vitro evaluation.

B., Pharamcological studies of 6 [D(-)-amino-p-hydroxyphenylacetamidol] penicillanic acid in humans. M., Comparative clinical pharmacology of amoxicillin and ampicillin administered orally. Kosmidis, J.; Willians, D.; Andrews, J., Amoxicillin - pharmacology, bacteriology and clinical studies.

K.;Turck, M., Amoxicillin, a new penicillin antibiotic. C., Antimicrobial activity and human pharmacology of amoxicillin. O., Nonlinearity of amoxicillin absorption kinetics in human. Simon, C.; Stille, W., Antibiotikatherapie in Klinik und Praxis. M.; Candler, E.L., Differential absorption of amoxicillin from the human small and large intestine. W.; Vergin, H., Improved high-performance liquid chromatographic determination of amoxicillin in human plasma by means of column switching. Hoizey, G.; Lamiable, D.; Frances, C.; Trenque, T.; Kaltenbach, M.; Denis, J.; Millart, H., Simultaneous determination of amoxicillin and clavulanic acid in human plasma by HPLC with UV detection. A.; Rayer, B., Bioequivalence study of a novel Solutab tablet formulation of amoxicillin/clavulanic acid versus the originator film-coated tablet. M., Sensitive assay for measuring amoxicillin in human plasma and middle ear fluid using solid-phase extraction and reversed-phase high-performance liquid chromatography.

J.; van Zijtveld, J., Determination of amoxicillin in human plasma by high-performance liquid chromatography and solid phase extraction. and Chulavatnatol, S., Simple analysis of amoxicillin in plasma by high performance liquid chromatography with internal standardization and ultraviolet detection.

Marscher, H.; Kikuta, C., Determination of amoxicillin in plasma by high-performance liquid chromatography with fluorescence after on-line oxidation.

A., Measurement of amoxicillin in plasma and gastric samples using high-performance liquid chromatography with fluorimetric detection.

J Chromatogr B Analyt Technol Biomed Life Sci , 774:141-8, 2002. Determination of ampicillin, amoxicillin, cephalexin, and cephradine in plasma by high-performance liquid chromatography using fluorometric detection.

and Westerlund, D., Automated determination of amoxicillin in biological fluids by column switching in ion-pair reversed phase liquid chromatographic systems with post-column derivation. H., Liquid chromatography-mass spectrometry in forensic and clinical toxicology. Henion, J.; Brewer, E.; Rule, G., Sample preparation for LC/ MS/MS: analyzing biological and enviromental samples.

B.; Sucupira, M.; Ilha, J.; De Nucci, G., Comparative bioavailability of 4 amoxicillin formulations in healthy human volunteers after a single dose administration. Int J Clin Pharm And Ther , v.39, 4: 167-172, 2001. Corresponding Author : Luis Renato Pires de Abreu, 288, Rua Simгo Ferreira Alves.

Published by the Canadian Society for Pharmaceutical Sciences. Kristina Duda, BSN, RN, CPN, has been working in healthcare since 2002. She specializes in pediatrics and disease and infection prevention. Michael Menna, DO, is a board-certified, active attending emergency medicine physician at White Plains Hospital in White Plains, New York.

Treatment Over the Counter Prevention Symptoms Common Cold Flu Related Illnesses.

If you or your child has ever needed to take an antibiotic for a bacterial infection, there's a good chance the medication prescribed was either amoxicillin or Augmentin (amoxicillin clavulanate).

A common assumption about these two medications is that Augmentin is simply a stronger version of amoxicillin but that isn't quite accurate. Augmentin contains a second active ingredient, which makes it more appropriate for treating certain infections than others.

The same holds true for amoxicillin and, to make the distinctions between the drugs even hazier, there are a few infections that both treat equally effectively.

Ultimately, the antibiotic a doctor prescribes will depend on the type of illness being treated and the bacteria responsible for it. Amoxicillin is often the first antibiotic prescribed for common bacterial infections, particularly those that cause illness in children, such as ear, nose, and throat infections, including tonsillitis. This antibiotic also is the first drug of choice for: Urinary tract infections Helicobacter pylori associated with ulcers Lyme disease. (Note that although amoxicillin can kill many of the same bacteria as penicillin, it is less effective than penicillin against Streptococcus pneumococcus, the bacteria commonly associated with meningitis and systemic bacteremia.) The side effects of amoxicillin tend to be relatively mild, which is another reason it's often prescribed for kids.

The most common ones include rash, vaginal itching, and a dark or "hairy tongue. ? ??Digestive side effects such as nausea and vomiting can occur, but are much more common with Augmentin. As with penicillin, there is a risk of an allergic reaction to amoxicillin in those predisposed to it. Symptoms include rash, itching, swelling of the face, tongue, and/or throat, trouble breathing, and dizziness.

It's vital a doctor take a medical history before prescribing amoxicillin to determine if a patient has a known history of allergy to antibiotics. Augmentin is amoxicillin combined with a beta-lactamase inhibitor called clavulanate, an ingredient that blocks the enzymes that contribute to antibiotic resistance. ? ? The addition of a beta-lactamase blocker to amoxicillin allows Augmentin to overcome resistance to harder-to-treat bacteria, broadening the spectrum of infections it can treat.

It is for this reason that Augmentin is referred to as a broad-spectrum antibiotic . Augmentin can treat the same bacteria as amoxicillin, but also is effective against certain harder-to-treat infections, ? ? including: Sinus infections Ear infections Bacterial infections associated with COPD Skin abscesses Diabetic foot. It should be noted there are a few infections for which amoxicillin and Augmentin are prescribed equally: Pyelonephritis (kidney infections) Erysipelas, a type of skin infection Chronic strep "carriers" The most common side effect of Augmentin is diarrhea. Some people may also experience nausea, vomiting, yeast infections, and rash.

If you have an infection and don't necessarily know which bacteria is causing it, it may seem to make sense to use an antibiotic that would kill the most bugs. ? ? Antibiotics used indiscriminately may destroy "good" bacteria along with "bad," thereby altering the body's natural flora and allowing even worse bacteria to proliferate.

Another, even more pressing concern is that using broad-spectrum antibiotics can lead to antibiotic resistance.

Resistance develops when an antibiotic you are using are unable to fully eradicate a bacteria in your body, ? ? often because you stopped treatment before you were supposed to. When this happens, a few mutated bacteria may survive, some of which may be naturally resistant to the antibiotic you were taking.