Assuntos
Eritromicina/metabolismo , Administração Oral , Adulto , Bile/metabolismo , Cápsulas , Eritromicina/administração & dosagem , Eritromicina/análogos & derivados , Estolato de Eritromicina/metabolismo , Ésteres , Humanos , Concentração de Íons de Hidrogênio , Injeções Intramusculares , Injeções Intravenosas , Cinética , Taxa de Depuração Metabólica , Veículos Farmacêuticos , Relação Estrutura-Atividade , ComprimidosAssuntos
Eritromicina/metabolismo , Administração Oral , Criança , Pré-Escolar , Orelha Média/metabolismo , Eritromicina/administração & dosagem , Eritromicina/análogos & derivados , Estolato de Eritromicina/administração & dosagem , Estolato de Eritromicina/metabolismo , Feminino , Humanos , Lactente , Cinética , Troca Materno-Fetal , Taxa de Depuração Metabólica , Tonsila Palatina/metabolismo , Veículos Farmacêuticos , Placenta/metabolismo , Gravidez , Saliva/metabolismo , Lágrimas/metabolismoRESUMO
The effect of erythromycin esteolate (EE) on bile flow and bile acid secretion was studied in male Wistar rats in vivo. Daily oral treatment with a dose of up to 100 mg/kg for 1 week increased the bile flow and the bile acid secretion. Increasing the days of treatment to 4 weeks with a dose of 20 mg/kg did not alter the measured parameters significantly. Acute intravenous injection of erythromycin lactobionate (50 mg/kg) also increased bile flow and biliary bile acid secretion temporarily. The increase in bile flow may partly be due to the osmotic effect of the drug and its metabolites in bile. Since EE failed to produce cholestasis in the range of therapeutic doses, rats do not seem to be a suitable experimental model for studying EE-cholestasis.
Assuntos
Colestase/induzido quimicamente , Estolato de Eritromicina/efeitos adversos , Eritromicina/análogos & derivados , Animais , Bile/efeitos dos fármacos , Bile/metabolismo , Ácidos e Sais Biliares/metabolismo , Estolato de Eritromicina/metabolismo , Masculino , Ratos , Ratos EndogâmicosRESUMO
We studied the pharmacokinetics of erythromycin estolate and ethylsuccinate suspensions in infants under 4 months of age who were being treated for chlamydial infections or pertussis. We conducted our studies after the initial dose of 10 mg/kg and subsequently during steady-state treatment. The estolate preparation resulted in higher peak concentrations in sera, and its absorption and elimination half-lives were longer. Peak concentrations occurred 3 h after a dose with the estolate preparation and 1 h after a dose with the ethylsuccinate preparation. The area under the curve for the estolate preparation was about three times greater than that for the ethylsuccinate preparation. Based on these findings, we recommend that erythromycin estolate suspensions be given to young infants at 8- or 12-h intervals (30 mg/kg per day in three divided doses or 20 mg/kg per day in two divided doses) and that erythromycin ethylsuccinate is best given at 6-h intervals (40 mg/kg per day in four divided doses).
Assuntos
Estolato de Eritromicina/metabolismo , Eritromicina/análogos & derivados , Infecções por Chlamydia/tratamento farmacológico , Eritromicina/sangue , Eritromicina/metabolismo , Eritromicina/uso terapêutico , Estolato de Eritromicina/sangue , Estolato de Eritromicina/uso terapêutico , Etilsuccinato de Eritromicina , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/tratamento farmacológico , Lágrimas/metabolismo , Coqueluche/tratamento farmacológicoRESUMO
In a 6-volunteer cross-over study the pharmacokinetics of 3 erythromycin preparations were compared. A single oral dose of 500 mg of each preparation was administered at each occasion and the levels measured in timed samples of plasma and saliva. Markedly higher blood concentrations of the estolate and propionate were obtained compared to the stearate. Comparison of serum and plasma concentration of the drugs from each split sample showed no significant differences. Plasma concentrations always exceeded those in saliva but for any one preparation a similar ratio was obtained at different times. This may be useful to ascertain compliance and to measure concentration of the compounds where direct measurement in plasma is not practicable.
Assuntos
Eritromicina/metabolismo , Saliva/metabolismo , Adulto , Química Farmacêutica , Eritromicina/sangue , Estolato de Eritromicina/metabolismo , Feminino , Meia-Vida , Humanos , Cinética , Masculino , Propionatos/metabolismo , Estearatos/metabolismoRESUMO
A randomized crossover study in 16 healthy volunteers given multiple doses of erythromycin base enteric-coated tablets or erythromycin estolate capsules revealed essentially no difference in the resultant plasma concentration of bioactive erythromycin. This similarity in bioactivity persisted despite the fact that total eryghromycin levels (bioactive erythromycin base plus bioinactive erythromycin propionate) were at least three times higher after administration of the estolate than after administration of the base.
Assuntos
Estolato de Eritromicina/metabolismo , Eritromicina/análogos & derivados , Eritromicina/metabolismo , Adulto , Disponibilidade Biológica , Cápsulas , Eritromicina/administração & dosagem , Estolato de Eritromicina/administração & dosagem , Feminino , Humanos , Masculino , Distribuição Aleatória , Comprimidos com Revestimento Entérico , Fatores de TempoRESUMO
A combined cholestatic and hepatocellular injury occurred in nine patients, following therapy with erythromycin estolate (EE) or other erythromycin derivatives. Eight of the nine patients developed jaundice within three weeks after initiation of treatment; pain was one of the main symptoms in five patients while fever and itching were noted in four patients. Symptoms and signs subsided and abnormal tests of liver function returned to normal after withdrawal of the drug. The major histologic finding was cholestasis, but the majority of cases also had evidence of hepatocellular injury of variable severity; one biopsy specimen showed centrilobular necrosis. Ultrastructural findings in one case included changes related to cholestasis as well as hepatocellular injury with striking mitochondrial abnormalities. Our data are compared with those of the literature, with special reference to morphologic features.
Assuntos
Colestase/induzido quimicamente , Estolato de Eritromicina/efeitos adversos , Eritromicina/análogos & derivados , Icterícia/induzido quimicamente , Fígado/efeitos dos fármacos , Adolescente , Adulto , Colestase/metabolismo , Colestase/patologia , Hipersensibilidade a Drogas , Estolato de Eritromicina/metabolismo , Feminino , Histocitoquímica , Humanos , Icterícia/metabolismo , Icterícia/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Mitocôndrias Hepáticas/ultraestrutura , Necrose , Grupos Raciais , Fatores de TempoRESUMO
The absorption, excretion, and metabolism of [1-14C]lauryl sulfate as either the sodium or propionyl erythromycin salt has been studied in the rat and man. In the rat 88% of the radiolabel from propionyl erythromycin [1-14C]lauryl sulfate was excreted in the urine in the 24-hr period following a single oral dose. More than 95% of the radiolabel was excreted as the metabolite butyric acid 4-sulfate. This metabolite was shown to be derived from carbons 1-4 of the lauryl sulfate moiety. There was no evidence of sulfate cleavage in the rat. In man 51-59% of the administered ratioactivity was recovered in the urine. The major excretion product was butyric acid 4-sulfate accounting for approximately 95% of urinary radioactivity. The remainder was unchanged lauryl sulfate. A significant portion of the radiolabeled propionyl erythromycin lauryl sulfate was converted to 14CO2 indicating that the sulfate linkage was cleaved. A minimum value of 9-16% of the dose was metabolized in this manner.
Assuntos
Estolato de Eritromicina/metabolismo , Eritromicina/análogos & derivados , Animais , Dióxido de Carbono/metabolismo , Cromatografia Gasosa , Deutério , Estolato de Eritromicina/urina , Fezes/análise , Humanos , Absorção Intestinal , Ácidos Láuricos/metabolismo , Masculino , Ratos , Fatores de TempoRESUMO
The absorption, excretion, and metabolism of propionyl erythromycin (PE) has been studied in the rat. The major routes of metabolism of PE are ester hydrolysis and N-demethylation. The rates of these two reactions have been examined in vivo using radiolabeled PE. The plasma half-life of the ester is 5.5 hr. The correlation of blood levels of radioactivity with 14CO2 production indicates that the ester is continually hydrolyzed after absorption. The half-life of the dimethyl-amino moiety of the desosamine sugar is estimated at 1.5 hr. This relatively short half-life compared to that of the ester is supported by the fact that at 3.5 hr after dosing there is twice as much desmethyl-PE in plasma as PE. After oral administration of either 14C-PE or 14C-erythromycin, 70% of the radioactivity is absorbed in 6 hr. The major route of excretion is via bile. Approximatley 40% of the absorbed dose is excreted in bile in the first 6 hr after dosing. Tissue levels of radioactivity after administration of 14C-erythromycin or 14C-PE indicate that PE or a metabolite accumulates in the tissue during chronic dosing, whereas erythromycin-related levels are similar after single or multiple doses.