RESUMO
The purpose of this study was to describe and compare the pharmacokinetic properties of different formulations of erythromycin in dogs. Erythromycin was administered as lactobionate (10 mg/kg, IV), estolate tablets (25 mg/kg p.o.) and ethylsuccinate tablets or suspension (20 mg/kg p.o.). After intravenous (i.v.) administration, the principal pharmacokinetic parameters were (mean +/- SD): AUC((0-infinity)) 4.20 +/- 1.66 microg x h/mL; C(max) 6.64 +/- 1.38 microg/mL; V(z) 4.80 +/- 0.91 L/kg; Cl(t) 2.64 +/- 0.84 L/h.kg; t((1/2)lambda) 1.35 +/- 0.40 h and MRT 1.50 +/- 0.47 h. After the administration of estolate tablets and ethylsuccinate suspension, the principal pharmacokinetic parameters were (mean +/- SD): C(max), 0.30 +/- 0.17 and 0.17 +/- 0.09 microg/mL; t(max), 1.75 +/- 0.76 and 0.69 +/- 0.30 h; t((1/2)lambda), 2.92 +/- 0.79 and 1.53 +/- 1.28 h and MRT, 5.10 +/- 1.12 and 2.56 +/- 1.77 h, respectively. The administration of erythromycin ethylsuccinate tablets did not produce measurable serum concentrations. Only the i.v. administration rendered serum concentrations above MIC(90) = 0.5 microg/mL for 2 h. However, these results should be cautiously interpreted as tissue erythromycin concentrations have not been measured in this study and, it is recognized that they can reach much higher concentrations than in blood, correlating better with clinical efficacy.
Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Estolato de Eritromicina/administração & dosagem , Estolato de Eritromicina/farmacocinética , Etilsuccinato de Eritromicina/farmacocinética , Administração Oral , Animais , Antibacterianos/sangue , Área Sob a Curva , Estudos Cross-Over , Cães , Formas de Dosagem , Estolato de Eritromicina/sangue , Etilsuccinato de Eritromicina/administração & dosagem , Etilsuccinato de Eritromicina/sangue , Feminino , Meia-Vida , Injeções Intravenosas , Modelos Lineares , Masculino , Taxa de Depuração MetabólicaRESUMO
A sensitive and selective liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for simultaneous identification and quantification of erythromycin ethylsuccinate and erythromycin in human plasma, which can be well applied to clinical study. The method was based on liquid-liquid extraction, followed by a LC procedure with an ODS C18 column, and mixture of acetonitrile and 1.67 mmol/l acetic acid as mobile phase. MS detection was performed using a single quadrupole mass spectrometer in positive selected ion monitoring (SIM) mode. The method was validated to be linear, precise and accurate. The lower limit of quantification of erythromycin ethylsuccinate and erythromycin were both 0.5 ng/ml. The proposed method enables the unambiguous identification and quantification of erythromycin ethylsuccinate and erythromycin for clinical drug monitoring.
Assuntos
Antibacterianos/sangue , Etilsuccinato de Eritromicina/sangue , Adulto , Antibacterianos/farmacocinética , Cromatografia Líquida de Alta Pressão , Etilsuccinato de Eritromicina/farmacocinética , Humanos , Indicadores e Reagentes , Masculino , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Plasma concentrations and pharmacokinetics of erythromycin and related compounds were determined after administration of erythromycin ethylsuccinate to six healthy male foals 3 to 5 months of age. Hay was withheld from the foals overnight and erythromycin ethylsuccinate (25 mg/kg of body weight) was administered intragastrically. Plasma erythromycin concentrations were determined at specific times after drug administration by high-performance liquid chromatography assay. Maximum peak plasma concentrations, time to maximum concentrations, area under plasma concentration versus time curves, elimination half-life, and mean residence time were determined from concentration versus time curves. Maximum peak concentration of erythromycin A (0.45 +/- 0.27 microg/ml) after administration of erythromycin ethylsuccinate was observed at 2.38 +/- 1.54 hours after treatment. Concentrations of anhydroerythromycin A were maximal at 2.2 +/- 2.0 hours and reached a maximum of 2.6 +/- 1.9 microg/ml. Plasma concentrations of the ester parent drug (erythromycin ethylsuccinate) were below the limit of quantitation (0.1 microg/ml) at all times except 2.5, 2.75, and 5.5 hours. Levels at those times ranged from 0.1 to 0.144 microg/ml. Erythromycin ethylsuccinate appears to be poorly absorbed after oral administration to fasted foals. Plasma concentrations of erythromycin A remained below 0.25 microg/ml (reported minimum inhibitory concentration for Rhodococcus equi) for less than 4 hours after intragastric administration of erythromycin ethylsuccinate, suggesting that the recommended dosage (25 mg/kg every 6 hours) would be suboptimal for treatment of R. equi infections.
Assuntos
Antibacterianos/farmacocinética , Etilsuccinato de Eritromicina/farmacocinética , Cavalos/sangue , Absorção , Administração Oral , Animais , Animais Lactentes , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Área Sob a Curva , Etilsuccinato de Eritromicina/administração & dosagem , Etilsuccinato de Eritromicina/sangue , MasculinoRESUMO
Relative bioavailability of erythromycin was determined after multiple-dose administration of erythromycin estolate in comparison to erythromycin ethylsuccinate both given as oral suspensions to twelve healthy volunteers. The daily erythromycin dose of erythromycin ethylsuccinate was 50% higher than the respective dose of erythromycin estolate; the dosage interval tau was 12 h for erythromycin estolate and 8 h for erythromycin ethylsuccinate. This scheme was planned in accordance to advices of the respective manufactures. Results of the study confirm the differences in extent of bioavailability of both erythromycin derivatives known from single-dose investigations. Furthermore, the experimental data show that a twice daily administration of 1000 mg erythromycin as erythromycin estolat resulted in sufficiently high plasma concentration of the active compound.
Assuntos
Estolato de Eritromicina/farmacocinética , Etilsuccinato de Eritromicina/farmacocinética , Adulto , Disponibilidade Biológica , Estudos Cross-Over , Método Duplo-Cego , Estolato de Eritromicina/administração & dosagem , Estolato de Eritromicina/sangue , Etilsuccinato de Eritromicina/administração & dosagem , Etilsuccinato de Eritromicina/sangue , Humanos , Projetos Piloto , Suspensões , Equivalência TerapêuticaRESUMO
A specific method for the determination of erythromycin 2'-ethylsuccinate (EM-ES) in plasma is described. The method involves a liquid-liquid extraction procedure followed by the analysis of extracts using phase-system switching (PSS) continuous-flow fast atom bombardment (CF-FAB) liquid chromatography-mass spectrometry (LC-MS). In PSS EM-ES is enriched after analytical separation on a short trapping column, from which it is desorbed to the LC-MS interface. In this way, favourable mobile phases can be used for the LC separation and for the MS detection. Using the PSS approach a flow-rate reduction from 1.0 ml/min in the LC system to 15 microliters/min going into the mass spectrometer was achieved without splitting. The determination limit for EM-ES was 0.1 microgram/ml.
Assuntos
Etilsuccinato de Eritromicina/sangue , Cromatografia Gasosa-Espectrometria de Massas/métodos , Pró-Fármacos/análise , Cromatografia Gasosa-Espectrometria de Massas/instrumentação , HumanosAssuntos
Antibacterianos/análise , Sítios de Ligação/efeitos dos fármacos , Ligação Competitiva , Animais , Bovinos , Meios de Cultura , Interações Medicamentosas , Etilsuccinato de Eritromicina/sangue , Etilsuccinato de Eritromicina/farmacologia , Hidrólise , Rim/análise , Fígado/análise , Pulmão/análise , Testes de Sensibilidade Microbiana , Músculos/análise , Neomicina/sangue , Neomicina/farmacologia , Oxitetraciclina/farmacologia , Pepsina A/farmacologia , Coelhos , Ovinos , Estreptomicina/farmacologiaAssuntos
Etilsuccinato de Eritromicina/análise , Neomicina/análise , Ágar , Animais , Bile/análise , Difusão , Etilsuccinato de Eritromicina/sangue , Etilsuccinato de Eritromicina/metabolismo , Etilsuccinato de Eritromicina/normas , Intestino Grosso/análise , Intestino Delgado/análise , Rim/análise , Pulmão/análise , Linfonodos/análise , Métodos , Músculos/análise , Miocárdio/análise , Neomicina/sangue , Neomicina/metabolismo , Neomicina/normas , Coelhos , Baço/análise , Estômago/análise , Língua/análiseAssuntos
Antibacterianos/uso terapêutico , Disenteria Bacilar/tratamento farmacológico , Lipídeos/sangue , Neomicina/uso terapêutico , Criança , Pré-Escolar , Etilsuccinato de Eritromicina/sangue , Etilsuccinato de Eritromicina/uso terapêutico , Humanos , Lactente , Insulina/biossíntese , Neomicina/sangueAssuntos
Antibacterianos/análise , Fígado/análise , Pulmão/análise , Pele/análise , Animais , Etilsuccinato de Eritromicina/administração & dosagem , Etilsuccinato de Eritromicina/análise , Etilsuccinato de Eritromicina/sangue , Etilsuccinato de Eritromicina/metabolismo , Imunodifusão , Injeções Subcutâneas , Masculino , Pomadas , Ratos , Fatores de TempoRESUMO
The serum and urine antibiotic levels in a group of 25 patients were determined after a single administration of a new antibiotic salt: erythromycin succinate of pyrrolidine-methyl-tetracycline. Some subjects were treated orally and other intramuscularly. The results obtained showed that this drug gives, both orally and intramuscularly, efficient serum and urine concentrations of tetracycline and erythromycin.