Assuntos
Carcinógenos , Animais , Relação Dose-Resposta a Droga , Camundongos , Ratos , Projetos de PesquisaRESUMO
The pharmacokinetics of netilmicin were examined in 25 adult subjects, 7 normal subjects, and 18 patients with renal impairment. Five were dialysis patients who were studied on and off dialysis. Netilmicin, 2 mg/kg, was infused intravenously over 1 h. The peak serum concentration ranged from 9 to 11 mug/ml. The mean biological half-life of netilmicin for subjects with a creatinine clearance (Ccr) > 70 ml/min was 2.7 h, for those with Ccr > 25 < 70 ml/min it was 10 h, for those with Ccr > 4 < 25 ml/min it was 32 h, and for those who were anephric it was 42 h. Ccr was correlated positively with the elimination constant and the drug's serum clearance. It was negatively correlated with the drug's volume of distribution. The dialyzer clearance of netilmicin was positively correlated with plasma flow rate and was similar to values previously reported for gentamicin. Netilmicin behaves in a fashion similar to other aminoglycosides. Therapeutic guidelines are suggested.
Assuntos
Gentamicinas/metabolismo , Nefropatias/metabolismo , Netilmicina/metabolismo , Diálise Renal , Adulto , Idoso , Feminino , Meia-Vida , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Bacteria and actinomycetes were screened for esterase enzymes capable of removing the para-nitrobenzyl ester from cephalosporins. An esterase preparation from Bacillus subtilis was used to prepare cephalexin and 7-ADCA from the corresponding para-nitrobenzyl esters.
Assuntos
Bactérias/enzimologia , Compostos de Benzil/metabolismo , Cefalosporinas/metabolismo , Esterases/metabolismo , Actinomyces/enzimologia , Bacillus subtilis/enzimologia , Cefalexina/isolamento & purificação , Cefalosporinas/isolamento & purificação , Esterases/isolamento & purificação , EsterificaçãoAssuntos
Preparações Farmacêuticas/metabolismo , Actinomycetales/metabolismo , Aminobutiratos/metabolismo , Encéfalo/enzimologia , Inibidores da Anidrase Carbônica/isolamento & purificação , Inibidores de Catecol O-Metiltransferase , Catecolaminas/metabolismo , Proteínas Inativadoras do Complemento , Meios de Cultura , AMP Cíclico/antagonistas & inibidores , Dopamina beta-Hidroxilase/antagonistas & inibidores , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos , Filtração , Fungos/metabolismo , Glucuronidase/antagonistas & inibidores , Antagonistas dos Receptores Histamínicos H1/isolamento & purificação , Modelos Biológicos , Inibidores da Monoaminoxidase/isolamento & purificação , Neuraminidase/antagonistas & inibidores , Preparações Farmacêuticas/classificação , Inibidores de Proteases , Espectrofotometria , Triptofano Hidroxilase/antagonistas & inibidores , Tirosina 3-Mono-Oxigenase/antagonistas & inibidoresAssuntos
Acridinas/metabolismo , Alcaloides/metabolismo , Antineoplásicos/metabolismo , Aspergillus/metabolismo , Streptomyces/metabolismo , Acridinas/farmacologia , Acridinas/uso terapêutico , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antivirais/síntese química , Antivirais/farmacologia , Herpesviridae/efeitos dos fármacos , Hidroxilação , Leucemia Experimental/tratamento farmacológico , Leucemia Mieloide/tratamento farmacológico , Camundongos , Mieloma Múltiplo/tratamento farmacológico , Neoplasias Experimentais/tratamento farmacológicoRESUMO
The possible role of a cephalosporin C acetyl esterase in the formation of the beta-lactam antibiotic A16886A, 7-(5-amino-5-carboxyvaleramido)-3-carbamoyloxy-methyl-3-cephem-4-carboxylic acid, by Streptomyces clavuligerus was studied. Addition of dl-valine-(14)C-1 to a fermentation of Cephalosporium acremonium gave cephalosporin C-(14)C-9 (I). The formation of deacetylcephalosporin C-(14)C-9 from I occurred at a greater rate in broths of S. clavuligerus than in the broths of C. acremonium, or in the autoclaved broths of S. clavuligerus. Diisopropylfluorophosphate partially inhibited the deacetylation of I in S. clavuligerus broth. An intracellular cephalosporin C esterase in S. clavuligerus could not be demonstrated. Although A16886A has been chemically synthesized from deacetylcephalosporin C, this reaction could not be demonstrated with S. clavuligerus.
Assuntos
Acetilesterase/metabolismo , Cefalosporinas/biossíntese , Streptomyces/enzimologia , Acilação , Carbamatos/biossíntese , Isótopos de Carbono , Meios de Cultura , Depressão Química , Isoflurofato/farmacologia , Éteres Metílicos/biossíntese , Concentração Osmolar , Streptomyces/efeitos dos fármacos , Streptomyces/metabolismoRESUMO
The incorporation of C-14 from amino acids into A16886B, 7-(5-amino-5-carboxyvaleramido)-7-methoxy-3-carbamoyloxymethyl-3-cephem-4- carboxylic acid, by Streptomyces clavuligerus is reported. As with cephalosporin C biosynthesis by the mold Cephalosporium acremonium, labels from cysteine, valine, and alpha-amino-adipic acid were incorporated. Unlike cephalosporin C, in A16886B label from lysine was incorporated into the alpha-aminoadipic acid side chain. Label from methionine-(14)C-methyl was incorporated into the methoxyl group. The relative percentage of incorporation of (3)H and (14)C from doubly labeled cystine suggests the improbability of the C-7 methoxyl group arising from an intermediate containing a double bond between C-6 and C-7.
Assuntos
Cefalosporinas/metabolismo , Streptomyces/metabolismo , Amidas/biossíntese , Aminoácidos/metabolismo , Isótopos de Carbono , Cefalosporinas/biossíntese , Cromatografia em Papel , Meios de Cultura , Hidrólise , Lactamas/metabolismo , Relação Estrutura-Atividade , TrítioRESUMO
Structural analysis of two new beta-lactam antibiotics, A16884A and A16886B, indicated that they, like cephalosporin C, were composed of modified valine and cysteine residues, and alpha-aminoadipic acid. However, acid hydrolysis of A16886B and A16884A produced three times as much glycine as did hydrolysis of cephalosporin C under the same conditions. Samples of A16886B-(14)C-6 and A16886B-(14)C-8 were prepared by the addition of cysteine-(14)C-3 and cystine-(14)C-1 to fermentations of Streptomyces clavuligerus. The specific activity of glycine obtained from hydrolysis of A16886B-(14)C-6 was considerably higher than that from hydrolysis of A16886B-(14)C-8. An explanation for the difference in amounts of glycine obtained from hydrolysis of these antibiotics is discussed.
Assuntos
Cefalosporinas , Glicina/síntese química , Carbamatos , Isótopos de Carbono , Cefalosporinas/isolamento & purificação , Cromatografia em Papel , Descarboxilação , Hidrólise , Indicadores e Reagentes , Éteres Metílicos , StreptomycesRESUMO
Claviceps purpurea has been shown to produce extracellular l-tryptophan from indole in stirred fermentors. The substrate specificity of this conversion was investigated by using substituted indoles, anthranilic acid, and 4-chloro-anthranilic acid. Addition of 2-, 4-, 5-, 6-, and 7-methyl indole or 6-chloroindole to C. purpurea C1M produced the corresponding substituted l-tryptophan. In contrast, addition of l-methyl, 6-trifluoromethyl, 6-nitro-, or 4-benzyloxy-substituted indoles, or anthranilic and 4-chloroanthranilic acids did not produce detectable amounts of the corresponding tryptophan.
Assuntos
Ascomicetos/metabolismo , Fermentação , Triptofano/biossíntese , Cromatografia em Camada Fina , Colorimetria , Meios de Cultura , Indóis/metabolismo , Triptofano/análise , ortoaminobenzoatos/metabolismoAssuntos
Alcaloides/biossíntese , Antibacterianos/biossíntese , Indóis/biossíntese , Oxepinas/biossíntese , Piperazinas/biossíntese , Ascomicetos/metabolismo , Aspergillus/metabolismo , Isótopos de Carbono , Di-Hidroxifenilalanina/metabolismo , Cetonas/biossíntese , Espectrometria de Massas , Fungos Mitospóricos/metabolismo , Penicillium/metabolismo , Fenilalanina/metabolismo , Sulfetos/biossíntese , Fatores de Tempo , Trítio , Tirosina/metabolismoRESUMO
Crude cell-free preparations of Botrytis cinerea were found to oxidize straight-chain primary alcohols (except methanol), aromatic primary alcohols, and unsaturated primary alcohols. The resulting products were the corresponding aldehydes and an equal molar quantity of hydrogen peroxide.