HPLC determination of amoxicillin comparative bioavailability in healthy volunteers after a single dose administration.

PURPOSE: An accurate, precise and sensitive HPLC assay was developed for the determination of amoxicillin in human plasma samples, to compare the bioavailability of two amoxicillin capsule (500mg) formulations (Amoxicilina from Brazil, as a test formulation and Amoxil from SmithKline Beecham Laboratories Ltda., Brazil, as a reference formulations) in 24 volunteers of both sexes. METHODS: Amoxicillin concentrations were analyzed by combined reversed phase liquid chromatography and UV detection (lambda=229 nm). Amoxicillin and cefadroxil (internal standard) were extracted from the plasma by addition of cold methanol. The separation was achieved using the Lichrosorb 10 microm, C18 reversed phase column at room temperature. The mobile phase consisted of a 95% phosphate buffer (0.01 mol/L), pH=4.8 and 5% acetonitrile mixture. The study was conducted using an open randomized 2-period crossover balanced design with a 1-week washout period between the doses. Plasma samples were obtained over an 8-hour period. The bioequivalence between the two formulations was assessed by calculating individual peak plasma concentrations (C(max) ) and area under the curve (AUC(0-8h) ) ratios (test/reference). The statistical interval proposed was 80-125%, as established by the US Food and drug administration Agency. RESULTS: The internal standard and amoxicillin eluted about 4.2 and 5.2 min, respectively at a flow rate of 1.3ml/min. The mean absolute recovery of AMO in plasma was 90.0% at 3 microg/ml, 98.6% at 25 microg/ml and 95.3 at 50 microg/ml. The assay showed excellent relationships between peak height ratios and plasma concentrations (r(2)>or= 0.999). The limit of quantification was 1g/ml, based on 200l of plasma. The geometric mean of Amoxicilina/Amoxil 500 mg capsules individual percentage ratio was 101.4% for AUC(0-8h), and 99.9% for C(max). The 90% confidence intervals were 98.3-104.4% and 95.7-103.9%, respectively. CONCLUSION: This simple, rapid and selective method is suitable for pharmacokinetic, bioavailability and bioequivalence studies. Since the 90% CI for both C(max )and AUC(0-8h) lies within the 80-125% interval proposed by the Food and Drug Administration, it was concluded that Amoxicilina 500 mg capsules was bioequivalent to Amoxil capsules 500 mg, in terms of both the rate and extent of absorption.

Comparative bioavailability of 4 amoxicillin formulations in healthy human volunteers after a single dose administration.

OBJECTIVE: To compare the bioavailability of two amoxicillin oral suspension (250 mg/5 ml) formulations and two amoxicillin capsule (500 mg) formulations (Amoxicilina from Medley S/A Indústria Farmaceûtica, Brazil, as test formulations and Amoxil from SmithKline Beecham Laboratórios Ltda., Brazil, as reference formulations) in 48 volunteers of both sexes. MATERIAL AND METHODS: The study was conducted open with a randomized two-period crossover design and a one-week washout period. Plasma samples were obtained over a 12-hour interval. Amoxicillin concentrations were analyzed by combined reversed phase liquid chromatography and tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using the selected ion monitoring method. From the amoxicillin plasma concentration vs. time curves the following pharmacokinetic parameters were obtained: AUC(last), AUC(0-infinity) and Cmax. RESULTS: Geometric mean of Amoxicilina/Amoxil 250 mg/5 ml individual percent ratio was 103.70% for AUC(last), 103.15% for AUC(0-infinity) and 106.79% for Cmax. The 90% confidence intervals were 97.82-109.94%, 97.40 to 109.24%, and 96.38-118.33%, respectively. Geometric mean of Amoxicilina/Amoxil 500 mg capsule individual percent ratio was 93.26% for AUC(last), 93.27% for AUC(0-infinity) and 90.74% for Cmax. The 90% confidence intervals were 85.0-102.33%, 85.12-102.31%, and 80.14-102.73%, respectively. CONCLUSION: Since the 90% CI for both Cmax, AUC(last) and AUC(0-inifnity) were within the 80-125% interval proposed by the Food and Drug Administration, it was concluded that Amoxicilina 250 mg/5 ml oral suspension and Amoxicilina 500 mg capsule were bioequivalent to Amoxil 250 mg/5 ml oral suspension and to Amoxil capsule 500 mg, respectively, with regard to both the rate and extent of absorption.

A pharmacodynamic model to support a 12-hour dosing interval for amoxicillin/sulbactam, a novel oral combination, in the treatment of community-acquired lower respiratory tract infections.

We evaluated, by time-kill studies, the pharmacodynamics of amoxicillin/sulbactam (AMX/SUL, 875 mg/125 mg), a novel oral combination, against the major respiratory pathogens in 12 volunteers receiving a single dose. The sera corresponding to 50% of a 12-h dosing interval displayed either bactericidal or inhibitory activity against both a penicillin-susceptible and a penicillin-intermediate Streptococcus pneumoniae strain (penicillin MIC of 0.03 and 0.25 microg/ml, respectively), as well as against a beta-lactamase-positive Moraxella catarrhalis and a beta-lactamase-negative Haemophilus influenzae strain. Both the peak samples and those corresponding to 4 h after dose (i.e. 33% of a 12-h dosing interval) proved active against both a penicillin-resistant S. pneumoniae (MIC, 2 microg/ml) and a beta-lactamase-positive H. influenzae strain. The AMX-SUL formulation evaluated in this study showed pharmacodynamic features that support clinical trials to assess its efficacy in the treatment of lower respiratory tract infections with a 12-h dosing interval regimen.