RESUMO
Feed and water components may interact with drugs and affect their dissolution and bioavailability. The impact of the vehicle of administration (feed and water) and the prandial condition of weaner piglets on amoxicillin´s oral bioavailability was evaluated. First, amoxicillin's in vitro dissolution and stability in purified, soft, and hard water, as well as release kinetics from feed in simulated gastric and intestinal media were assessed. Then, pharmacokinetic parameters and bioavailability were determined in fasted and fed pigs using soft water, hard water, or feed as vehicles of administration following a balanced incomplete block design. Amoxicillin showed similar dissolution profiles in soft and hard water, distinct from the dissolution profile obtained with purified water. Complete dissolution was only achieved in purified water, and merely reached 50% in soft or hard water. Once dissolved, antibiotic concentrations decreased by around 20% after 24 h in all solutions. Korsmeyer-Peppas model best described amoxicillin release from feed in simulated gastric and intestinal media. Feed considerably reduced antibiotic dissolution in both simulated media. In vivo, amoxicillin exhibited significantly higher bioavailability when delivered via water to fasted than to fed animals, while in-feed administration yielded the lowest values. All treatments showed a similar rate of drug absorption. In conclusion, we demonstrated that water and feed components, as well as feed present in gastrointestinal tract of piglets decrease amoxicillin´s oral bioavailability. Therefore, the use of oral amoxicillin as a broad-spectrum antibiotic to treat systemic infections in pigs should be thoroughly revised.
Assuntos
Amoxicilina , Ração Animal , Antibacterianos , Disponibilidade Biológica , Animais , Amoxicilina/farmacocinética , Amoxicilina/administração & dosagem , Amoxicilina/sangue , Ração Animal/análise , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Administração Oral , Suínos , Água/química , Masculino , FemininoRESUMO
AIMS: To evaluate the relative bioavailability of oral amoxicillin (AMX) tablets in comparison to AMX suspension in Roux-en-Y gastric bypass bariatric subjects. METHODS: A randomized, double-blind, cross-over study was performed on the bioavailability of oral AMX tablets and suspension in Roux-en-Y gastric bypass subjects operated at least 3 months previously . Doses of 875 mg of the AMX tablet or 800 mg of the AMX suspension were given to all the subjects, allowing a washout of 7 days between the periods. Blood samples were collected at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6 and 8 hours after drug administration and the AMX levels were quantified by liquid chromatography coupled with triple quadrupole tandem mass spectrometry. The pharmacokinetic parameters were calculated by noncompartmental analysis, normalized to an 875 mg dose and the bioavailability of the AMX from the tablets was compared to that from the suspension formulation. RESULTS: Twenty subjects aged 42.65 ± 7.21 years and with a body mass index of 29.88 ± 4.36 kg/m2 were enrolled in the study. The maximum AMX plasma concentration of the tablets and the suspension (normalized to 875 mg) were 7.42 ± 2.99 mg/L and 8.73 ± 3.26 mg/L (90% confidence interval of 70.71-99.11), and the total area under the curve from time zero to infinity were 23.10 ± 7.41 mg.h/L and 27.59 ± 8.32 mg.h/L (90% confidence interval of 71.25-97.32), respectively. CONCLUSION: The tablets presented a lower bioavailability than the suspension formulation and the total absorbed amount of AMX in these subjects was lower in comparison to the standard AMX absorption rates in nonbariatric subjects, regardless of the formulation.
Assuntos
Amoxicilina/farmacocinética , Antibacterianos/farmacocinética , Derivação Gástrica/efeitos adversos , Administração Oral , Adulto , Amoxicilina/administração & dosagem , Amoxicilina/sangue , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Área Sob a Curva , Disponibilidade Biológica , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Suspensões , ComprimidosRESUMO
BACKGROUND: Bariatric surgery leads to several anatomo-physiological modifications that may affect pharmacokinetic parameters and consequently alter the therapeutic effect of drugs, such as antibiotics. The pharmacokinetics of oral amoxicillin after Roux-en-Y gastric bypass (RYGB) surgery is unknown. OBJECTIVES: The objective of this study was to evaluate the impact of bariatric surgery on the pharmacokinetics of amoxicillin. METHODS: This study was performed as a randomized, open-label, single-dose clinical trial, with two periods of treatment, in which obese subjects (n = 8) received an amoxicillin 500 mg capsule orally before and 2 months after the RYGB surgery. The amoxicillin plasma concentration was determined by liquid chromatography coupled to mass spectrometry (LC-MS/MS). RESULTS: After the surgery, the mean weight loss was 17.03 ± 5.51 kg, and mean body mass index (BMI) decreased from 46.21 ± 2.82 to 38.82 ± 3.32 kg/m2. The mean amoxicillin area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration (AUC0-tlast) increased significantly (3.5-fold); the maximum plasma concentration (Cmax) increased 2.8-fold after the bariatric surgery. No correlation was found between amoxicillin absorption, BMI, and weight loss percentage. CONCLUSION: The alterations observed in the amoxicillin pharmacokinetics suggest that obese subjects included in this trial had a substantially increase in amoxicillin systemic exposure after RYGB surgery. However, despite this increase, its exposure was lower than the values reported for non-obese volunteers. TRIAL REGISTRATION: Identifiers: NCT03588273.
Assuntos
Amoxicilina/farmacocinética , Antibacterianos/farmacocinética , Derivação Gástrica , Obesidade Mórbida/metabolismo , Obesidade Mórbida/cirurgia , Redução de Peso/fisiologia , Administração Oral , Adulto , Amoxicilina/administração & dosagem , Amoxicilina/sangue , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Índice de Massa Corporal , Cromatografia Líquida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Espectrometria de Massas em TandemRESUMO
PURPOSE: To compare the pharmacokinetic profiles and to evaluate the bioequivalence of two commercial amoxicillin suspension formulations (500 mg/5 mL AMOXIL®, reference formulation and AMOXI-PED®, test formulation) in healthy Brazilian volunteers. METHODS: Under fasting condition, 25 volunteers (13 males and 12 females) were included in this randomized, open-label, two-period crossover (1-week washout interval) bioequivalence study. Blood samples were collected at pre-dose (0 hour) and 0.5, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 12 hours after drug ingestion. Pharmacokinetic parameters (Cmax, tmax, t1/2, AUC0-tlast, and AUC0-∞) were calculated from plasma concentrations for both formulations in each subject. RESULTS: Arithmetic mean values of the pharmacokinetic parameters were: Cmax = 12.004 (± 2.824) µg×mL-1; tmax = 1.118 (± 0.396) h; t1/2 = 1.226 (± 0.179) h; AUC0-tlast = 29.297 (± 6.007) µg×h×mL-1; and AUC0-∞ = 29.299 (± 6.007) µg×h×mL-1 for reference formulation and Cmax = 11.456 (± 2.825) µg×mL-1; tmax = 1.331 (± 0.509) h; t1/2 = 1.141 (± 0.133) h; AUC0-tlast = 28.672 (± 5.778) µg×h×mL-1; and AUC0-∞ = 28.693 (± 5.796) µg×h×mL-1 for test formulation. The confidence intervals (90% CI) for reference and test formulations were, respectively, 90.74 - 100.46% for Cmax and 93.62 - 103.61% for AUC0-t. CONCLUSION: Based on the results, both formulations of amoxicillin evaluated in this study were considered bioequivalent according to FDA and ANVISA/Brazil criteria.
Assuntos
Amoxicilina/farmacocinética , Antibacterianos/farmacocinética , Adulto , Amoxicilina/administração & dosagem , Amoxicilina/sangue , Amoxicilina/química , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Antibacterianos/química , Área Sob a Curva , Brasil , Química Farmacêutica , Estudos Cross-Over , Jejum/sangue , Feminino , Meia-Vida , Voluntários Saudáveis , Humanos , Masculino , Taxa de Depuração Metabólica , Suspensões , Equivalência Terapêutica , Adulto JovemAssuntos
Amoxicilina/farmacocinética , Antibacterianos/farmacocinética , Antieméticos/farmacologia , Cães/sangue , Metoclopramida/farmacologia , Administração Oral , Amoxicilina/administração & dosagem , Amoxicilina/sangue , Animais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Antieméticos/administração & dosagem , Esquema de Medicação/veterinária , Interações Medicamentosas , Meia-Vida , Taxa de Depuração Metabólica/efeitos dos fármacos , Metoclopramida/administração & dosagemRESUMO
Amoxicillin-sulbactam (AMX-SUL) is an aminopenicillin/beta-lactamase inhibitor combination currently available in 29 countries which may be a suitable option for treating intra-abdominal infections. the aim of this study was to identify the optimal dose and ratio between components of this formulation through an ex-vivo human pharmacodynamic model against Escherichia coli. Four volunteers were randomized to receive alternatively a single dose of AMX-SUL infused either over 30 min or 3h in the following ratios (g/g): 1/0.5; 1/1, 2/0.5 and 0/2. time-kill studies were performed with the 0-, 0.5-, 2-, 4-, 6- and 8-h post-dosing sera against E. coli ATCC 25922 (AMX MIC, 2 microg/ml; AMX-SUL MIC, 2 microg/ml) and E. coli ATCC 35218 (AMX MIC, 1024 microg/ml; AMX-SUL MIC, 4-8 microg/ml). AMX-SUL 1g/0.5 g infused over 30 min was only active at 0.5 h after dose, being inferior to both AMX-SUL 1g/1g and AMX-SUL 2g/0.5 g against E. coli ATCC 25922, for which the 2h post-dose serum proved active. When tested against E. coli ATCC 35218, AMX-SUL 1g/0.5 g and AMX-SUL 2g/0.5 g were active only at 0.5 h post-dose, whereas AMX-SUL 1g/1g showed bactericidal activity 0.5h post-dose and was able to inhibit bacterial growth 2 h post-dose. When infused over 3h, the antimicrobial activity of AMX-SUL was better than the 30-min infusion. Moreover, AMX-SUL 1g/1g was able to inhibit, and kill to some extent, the E. coli ATCC 25922 strain at 4h post-dose (i.e. 67% and 50% of a 6- and 8-h dosing interval, respectively). The present study suggests that 1g/1g is the best formulation for AMX-SUL against E. coli. The infusion over 3h optimizes its pharmacodynamic profile, as well as that of the 1g/0.5g combination. These findings encourage the performance of clinical trials to assess the efficacy of this combination, given as an extended infusion, in the treatment of community-acquired intra-abdominal infections.
Assuntos
Amoxicilina/administração & dosagem , Infecções por Escherichia coli/tratamento farmacológico , Sulbactam/administração & dosagem , Adulto , Amoxicilina/sangue , Atividade Bactericida do Sangue , Estudos Cross-Over , Combinação de Medicamentos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Método Simples-Cego , Sulbactam/sangue , Fatores de TempoRESUMO
A simple, fast, sensitive and selective solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) method for the quantitative analysis of ampicillin (CAS 69-53-4) in human plasma was developed using amoxicillin as internal standard, and sample extraction by solid-phase extraction (SPE). Extracts were separated by reversed-phase C18 with aqueous mobile phase (acetonitrile, 80:20, v/v) with 0.1% formic acid. The method was validated and successfully applied in a bioequivalence study of capsules 500 mg of ampicillin. Using a short running time of 2.5 min, the lower limit of quantification (LLOQ) for obtained ampicillin was 0.1 microg/ml for a plasma sample of 250 microl and a recovery of 94.38% +/- 4.05. Bioequivalence between the products was determined by calculating 90% confidence intervals (CI) for the ratio of Cmax, AUC0-t and AUC0-inf values for the test and reference products, which were within the 0.80-1.25 interval proposed by FDA and EMEA. It is concluded that the two formulations are bioequivalent in their rate and extent of absorption, and thus, may be used interchangeably.
Assuntos
Ampicilina/sangue , Ampicilina/farmacocinética , Antibacterianos/sangue , Antibacterianos/farmacocinética , Adolescente , Adulto , Amoxicilina/sangue , Calibragem , Cromatografia Líquida , Estudos Cross-Over , Método Duplo-Cego , Humanos , Indicadores e Reagentes , Masculino , Controle de Qualidade , Reprodutibilidade dos Testes , Extração em Fase Sólida , Espectrometria de Massas em Tandem , Equivalência TerapêuticaRESUMO
A simple, precise, and reliable chromatographic method was developed for the simultaneous determination in plasma and infected tissue of five antimicrobials proposed for the treatment of actinomycotic mycetoma: amoxicillin, trimethoprim, linezolid, sulfamethoxazole and garenoxacin. Separation of the analytes was achieved on an Atlantis dC18 column (150 mm x 4.6 mm, ID 5 microm) with a mobile phase composed of acetonitrile and trifluoroacetic acid (ATF) 0.1% (v/v) using a gradient program. The detection was carried out using a diode array detector at 254 nm and in a fluorescence detector at wavelengths of excitation and emission of 292 nm and 392 nm for linezolid and sulfamethoxazole, and 292 nm and 408 nm for garenoxacin, respectively. The intraday precision was in the range of 0.7-15% of relative standard deviations (%R.S.D.) for plasma and 1-18% for tissue. Linearity range was from 2.4 to 20 microg/ml for amoxicillin, 0.3 to 20 microg/ml for trimethoprim, sulfamethoxazole and linezolid, and 0.3 to 10 microg/ml for garenoxacin. Acetonitrile was used to precipitate proteins from plasma. Recoveries in plasma ranged from 71% to 118% and in infected tissue from 78% to 122%. Limits of detection (LODs) were 1.2 and 0.5 microg/ml for amoxicillin in plasma and tissue, respectively and 0.15 and 1.2 microg/ml in plasma and tissue, respectively for the other antimicrobials. The method can be applied for individual or simultaneous determination of the antimicrobials in plasma and tissue of mouse infected with actinomycetoma.
Assuntos
Antibacterianos/análise , Antibacterianos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Micetoma/tratamento farmacológico , Espectrometria de Fluorescência/métodos , Acetamidas/análise , Acetamidas/sangue , Acetonitrilas/química , Amoxicilina/análise , Amoxicilina/sangue , Animais , Soluções Tampão , Precipitação Química , Estabilidade de Medicamentos , Fluoroquinolonas/análise , Fluoroquinolonas/sangue , Congelamento , Concentração de Íons de Hidrogênio , Linezolida , Camundongos , Oxazolidinonas/análise , Oxazolidinonas/sangue , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sulfametoxazol/análise , Sulfametoxazol/sangue , Fatores de Tempo , Trimetoprima/análise , Trimetoprima/sangue , Água/químicaRESUMO
The aim of this study was to evaluate the effect of sodium diclofenac on the bioavailability of amoxicillin. In this randomised, crossover study with a 1-week washout period, 20 volunteers received a 2g oral dose of amoxicillin (Amoxil) (Group 1) or a 2g oral dose of amoxicillin with 100 mg of sodium diclofenac (Voltaren) (Group 2). Blood samples were collected at 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24h following drug administration. High-performance liquid chromatography with ultraviolet detection was used to quantify plasma amoxicillin concentrations. Bioassay (Micrococcus luteus ATCC 9341) was performed to verify the antimicrobial efficacy of amoxicillin in vitro. The pharmacokinetic parameters area under the plasma concentration-time curve (AUC), maximum plasma concentration observed during the 24-h study period (C(max)) and renal clearance (CL) were analysed by analysis of variance, and time at which C(max) occurred (T(max)) and volume of distribution (VD) were analysed by Wilcoxon test (P<0.05). For Group 1, the mean (+/- standard deviation) AUC(0-24), C(max) and T(max) values were 3391.8+/-1186.7 microg min/mL, 17.3+/-6.5 microg /mL and 121.5+/-20.6 min, respectively; and for Group 2, the values were 2918.4+/-1024.8 microg min/mL, 15.5+/-5.8 microg /mL and 136.5+/-30.0 min, respectively. Lower values of AUC and C(max) were observed for Group 2 (P<0.05). CL of amoxicillin increased (P< 0.05) by 18.5% in Group 2, suggesting that sodium diclofenac may interfere with amoxicillin renal excretion. In conclusion, sodium diclofenac can significantly reduce the bioavailability of amoxicillin.
Assuntos
Amoxicilina/farmacocinética , Diclofenaco/farmacologia , Adulto , Amoxicilina/sangue , Disponibilidade Biológica , Estudos Cross-Over , Diclofenaco/sangue , Diclofenaco/farmacocinética , Interações Medicamentosas , Humanos , MasculinoRESUMO
OBJECTIVE: To compare the bioavailability of amoxicillin 875 mg tablets (EMS Sigma Pharma used as test formulation) and Amoxil BD 875 mg tablets (GlaxoSmithKline used as reference formulation) in 26 healthy volunteers. MATERIAL AND METHODS: 26 healthy volunteers (13 males and 13 females) received each formulation in an open, 2 x 2 crossover, randomized study with seven days of washout period between doses. Plasma samples were obtained over a 12-hour interval after administration. Plasmatic amoxicillin concentrations were obtained by combined reversed-phase liquid chromatography and mass spectrometry with positive ion electrospray ionization using the select ion monitoring method. AUC was calculated by the trapezoidal rule extrapolation method. Cmax and tmax were compiled from the plasmatic concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC0-inf, AUC0-12 h, Cmax and untransformed tmax. RESULTS: The mean values (+/- SD) for AUC0-12 h (microg x h x ml(-1)), AUC0-inf (microg x h x ml(-1)), Cmax (microg x ml(-1)), t1/2 (h) and tmax (h), were, respectively: 55.42 (+/- 16.85), 55.42 (+/- 16.85), 18.59 (+/- 6.3), 1.49 (+/- 1.57) and 2.04 (+/- 0.75) concerning the test formulation, and 51.11 (+/- 18.9), 51.29 (+/- 19.12), 17.83 (+/- 5.86), 1.52 (+/- 1.31) and 2.02 (+/- 0.87) concerning the reference formulation. Confidence intervals (90%) of amoxicillin means of AUC0-12 h and Cmax ratios (test/reference) were: 0.961-1.149 and 0.914-1.142, respectively, agreeing with the bioequivalence criteria established by the Brazilian National Health Surveillance Agency. CONCLUSION: Both formulations were bioequivalent based on both the rate and extent of absorption.
Assuntos
Amoxicilina/farmacocinética , Antibacterianos/farmacocinética , Administração Oral , Adulto , Amoxicilina/administração & dosagem , Amoxicilina/sangue , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida , Estudos Cross-Over , Feminino , Meia-Vida , Cefaleia/induzido quimicamente , Humanos , Masculino , Náusea/induzido quimicamente , Espectrometria de Massas por Ionização por Electrospray , Comprimidos , Equivalência Terapêutica , Fatores de TempoRESUMO
We designed a 4-way crossover, ex-vivo pharmacodynamic study to compare the bactericidal rate of amoxicillin/sulbactam (AMX-SUL), azithromycin (AZM), doxycycline (DOX) and levofloxacin (LVX) against Streptococcus pneumoniae ATCC 49619. Six volunteers were randomized to receive alternatively a single tablet of the above drugs. Venous blood samples were obtained immediately before and at 2, 4 and 6 h after dose to perform time-kill studies and to determine antibiotic levels in serum. AMX-SUL was the only drug showing bactericidal activity with the sera obtained at every time after dose, as defined by a > or = 3-log10 cfu/ml decrease in the viable cell counts compared to the original inoculum after a 24-h incubation. AZM was only inhibitory at 2h after dose (i.e. a 1.3-log10 cfu/ml decrease in the viable cell counts) and proved bactericidal at 4 and 6 h post-dose. LVX proved bactericidal with the 2-h serum, was only inhibitory with the 4-h serum (e.g. a 1.5-log10 cfu/ml decrease) and was unable to avoid bacterial growth at 6 h post-dose. Bacterial growth was observed with DOX at every time after dose. This study may shed light on the understanding of breakthrough pneumococcal bacteremia during the course of oral therapy with AZM in patients with community-acquired nia (CAP), as well as the increasing treatment failures observed with LVX, and the selection of bacterial resistance during therapy reported with both drugs. It also provides the basis for a "warning signal" on the use of oral DOX and confirms the efficacy of AMX-SUL.
Assuntos
Amoxicilina/farmacologia , Azitromicina/farmacologia , Doxiciclina/farmacologia , Levofloxacino , Ofloxacino/farmacologia , Streptococcus pneumoniae/efeitos dos fármacos , Sulbactam/farmacologia , Adulto , Amoxicilina/sangue , Análise de Variância , Azitromicina/sangue , Atividade Bactericida do Sangue , Contagem de Colônia Microbiana , Estudos Cross-Over , Doxiciclina/sangue , Farmacorresistência Bacteriana , Quimioterapia Combinada/uso terapêutico , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Ofloxacino/sangue , Probabilidade , Sensibilidade e Especificidade , Teste Bactericida do Soro , Método Simples-Cego , Estatísticas não Paramétricas , Streptococcus pneumoniae/isolamento & purificação , Sulbactam/sangueRESUMO
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.
Assuntos
Amoxicilina/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Penicilinas/farmacocinética , Amoxicilina/sangue , Disponibilidade Biológica , Estudos Cross-Over , Feminino , Humanos , Masculino , Penicilinas/sangue , Padrões de ReferênciaRESUMO
This work reports the use of multidimensional HPLC by coupling a restricted access medium (RAM) bovine serum albumin (BSA) octadecyl column (100 x 4.6 mm I.D., 10 microm particle size and 120 A pore size) to an octadecyl Hypersil column (150 x 4.6 mm I.D., 5 microm particle size and 120 A pore size) to the analysis of amoxycillin in human plasma by direct injection. Ion pairing was necessary to extract amoxycillin with good recovery from the plasma proteins. To prepare the spiked samples, aliquots (60 microl) of the appropriated standard solutions were added to each culture tube containing an 180 microl of plasma and a solution of 0.30 mM tetrabuthylammonium phosphate (60 microl). They were vortexed for 15 s and then 290 microl were transferred to autosampler vials. Aliquots (250 microl) of the spiked plasma samples were injected to a column-switching HPLC system. An analysis time of 25 min with no time spent on sample preparation was achieved. The developed method showed good selectivity, sensitivity, accuracy and precision for direct analysis of this polar low wavelength ultraviolet absorption antibiotic using only 180 microl of human plasma. The validated method proved to be reliable and sensitive for the determination of amoxycillin in plasma samples of five healthy volunteers to whom test and reference formulations were administered as an oral dose (500 mg).
Assuntos
Amoxicilina/sangue , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/instrumentação , Humanos , Reprodutibilidade dos Testes , Espectrofotometria UltravioletaRESUMO
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.
Assuntos
Amoxicilina/farmacocinética , Química Farmacêutica , Penicilinas/farmacocinética , Administração Oral , Adulto , Amoxicilina/sangue , Disponibilidade Biológica , Cápsulas , Cromatografia Líquida , Estudos Cross-Over , Feminino , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Penicilinas/sangueRESUMO
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.
Assuntos
Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Quimioterapia Combinada/administração & dosagem , Penicilinas/administração & dosagem , Infecções Respiratórias/tratamento farmacológico , Sulbactam/administração & dosagem , Administração Oral , Adulto , Amoxicilina/sangue , Amoxicilina/farmacocinética , Antibacterianos/sangue , Antibacterianos/farmacocinética , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada/sangue , Quimioterapia Combinada/farmacocinética , Feminino , Infecções por Haemophilus/sangue , Infecções por Haemophilus/tratamento farmacológico , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/isolamento & purificação , Humanos , Masculino , Modelos Biológicos , Moraxella catarrhalis/efeitos dos fármacos , Moraxella catarrhalis/isolamento & purificação , Infecções por Neisseriaceae/sangue , Infecções por Neisseriaceae/tratamento farmacológico , Infecções por Neisseriaceae/microbiologia , Penicilinas/sangue , Penicilinas/farmacologia , Infecções Pneumocócicas/sangue , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/microbiologia , Infecções Respiratórias/sangue , Infecções Respiratórias/microbiologia , Teste Bactericida do Soro , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , Sulbactam/sangue , Sulbactam/farmacocinéticaRESUMO
Se comparó en un estudio al azar y en forma ciega la respuesta a la combinación de ambroxol-amoxicilina (tratamiento A) vs amoxicilina sola (tratamiento B) por vía oral en un grupo de 40 pacientes adultos, que cursaban con infecciones bacterianas del tracto respiratorio bajo. Se incluyeron sujetos de 20 a 55 años de edad, masculinos y femeninos con medias de 40.5 años para el grupo A y de 34.5 para el grupo B. Se consideró como índice de mejoría temprana la desaparición de la fiebre y como curación la desaparición de los signos clínicos o paraclínicos en el enfermo. Se cultivó la expectoración en todos los casos y se realizó antibiograma. La concentración del antibiótico en sangre y moco se determinaron por medio de bioensayo con cultivos de Sarcina lútea en todos los pacientes. Se compararon los dos grupos de tratamiento para la desaparición de síntomas, mejoría de la infección y diferencias en la concentración del antibiótico en la sangre y moco. Se analizaron las diferencias por la prueba de Wilcoxon para muestras pareadas y ANOVA unidireccional (prueba de Kruskall-Wallis). Finalmente se identificaron las variables asociadas a la mejoría temprana por un modelo de regresión lineal múltiple por pasos y un modelo de regresión logística múltiple. Al compararse con la prueba de Wilcoxon se encontraron diferencias significativas a favor de la combinación de ambroxol y amoxicilina para las concentraciones del antibiótico en sangre y moco (p=0.00021), y para la desaparición de la fiebre (p=0.00036), esto fue confirmado por las pruebas de ANOVA. Por este método se encontró una diferencia marginal en las cifras de leucocitos al inicio a favor de los pacientes del grupo A (p=0.02). Al aplicarse el modelo de regresión lineal, la única variable que se ajustó adecuadamente, fueron las concentraciones del antibiótico en el moco. Con esto podemos concluir que en los pacientes tratados con la combinación de ambroxol-amoxicilina, los niveles del antibiótico en sangre y moco son más altos y su mejoría clínica es significativamente más temprana. Esta mejoría parece estar dada por las altas concentraciones del antibiótico en el moco de la expectoración, por lo que el efecto sinérgico del ambroxol en la amoxicilina, establece una diferencia notable que haría deseable el uso de la combinación en pacientes seleccionados con infecciones respiratorias bacterianas.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Ambroxol/sangue , Amoxicilina/sangue , Infecções Respiratórias/sangue , Ambroxol/uso terapêutico , Amoxicilina/uso terapêutico , Combinação de Medicamentos , México , Muco , Infecções Respiratórias/tratamento farmacológicoRESUMO
Existen publicados en la literatura internacional, diversos estudios cuidadosamente elaborados, que han valorado la influencia decisiva del nuevo mucolítico clorhidrato de trans-4-[(2-amino-3-5-dibromobencil)amino]-ciclohexanol (ambroxol) sobre la actividad del P-hidroxiderivado de la alfa-aminobecil penicilina (amoxacilina) cuando se administran asociados. Esta asociación produce un marcado efecto sinérgico, aumentando significativamente los niveles del antibiótico en los líquidos broncopulmonares, así como incrementando su penetración en el tejido pulmonar. Los reportes de Spátula1, Wiemeyer2 y Gené3 apoyan este sinergismo. En base a esto se diseñó un estudio para valorar la eficacia de la combinación en el tratamiento de las infecciones de vías respiratorias bajas en niños y la distribución del antibiótico en suero y moco broncopulmonar utilizando un método de lavado bronquial simplificado. Se estudiaron 20 menores que ingresaron consecutivamente al servicio de medicina del Hospital Infantil Aragón, siendo el 45 porciento varones y 55 porciento mujeres. Sus edades variaron de cuatro a once años. Todos presentaron un episodio infeccioso agudo de vías respiratorias siendo el 60 porciento bronquitis, 20 porciento neumonía, 10 porciento absceso pulmonar, y 10 porciento bronquiectasias infectadas. Se les ingresó al azar en dos grupos de tratamiento después de habérseles realizado historia clínica y evaluación de laboratorio y gabinete completas. A todos se les practicó lavado bronquial con frotis y cultivo de expectoración y se les inició tratamiento intrahospitalario con amoxicilina sola o la combinación de ambroxol-amoxicilina, a dosis de 50 mg del antibiótico por kg de peso/día divididos en tres dosis cada ocho horas durante 10 días. Se encontró una diferencia ampliamente significativa en las concentraciones del antibiótico en suero y moco de los pacientes que recibieron la combinación (p < 0.0001) aunque no podemos explicar el mecanismo involucrado en los niveles séricos.