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1.
Pharmacol Res Perspect ; 9(2): e00746, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33764686

RESUMO

This study sought to investigate whether dosing frequency (the number of doses per day) affects the antimicrobial efficacy and safety of ampicillin/sulbactam (ABPC/SBT) in Japanese elderly pneumonia patients treated with ABPC/SBT at 6 g/day. This was a retrospective observational study that included hospitalized elderly patients (aged ≥75 years, 10 ml/min ≤CLcr <50 ml/min) who received 3 g every 12 h (BID; n = 61) or 1.5 g every 6 h (QID; n = 45) for the treatment of pneumonia. The primary endpoint was clinical response, assessed by measuring body temperature, white blood cell count, and C-reactive protein levels. Pharmacokinetic and pharmacodynamic simulations were conducted in silico to rationalize the clinical findings. The clinical response rates (extremely effective and effective) in the BID and QID groups were 36.1% and 55.6%, respectively (p = .0459). QID tended to be more effective in patients with gram-negative rods detected (p = .0563). According to the simulated minimum plasma ABPC concentrations at steady state for BID and QID were 2.5 and 7.3 µg/ml, respectively (p < .0001). Based on the simulated time above minimum inhibitory concentration (MIC), pharmacological (not clinical) efficacy was predicted to be higher with QID. Both groups had similar safety profiles. The main adverse event in both groups was liver damage. The present retrospective survey demonstrated that ABPC/SBT treatment for elderly patients with pneumonia and renal dysfunction was more effective with QID than with BID. Therefore, the QID regimen is worthy of consideration to improve the clinical outcomes of ABPC/SBT therapy in the present patient population.


Assuntos
Antibacterianos/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Pneumonia Bacteriana/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Ampicilina/administração & dosagem , Ampicilina/efeitos adversos , Ampicilina/farmacocinética , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Simulação por Computador , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Taxa de Filtração Glomerular , Humanos , Injeções Intravenosas , Masculino , Eliminação Renal , Estudos Retrospectivos , Sulbactam/administração & dosagem , Sulbactam/efeitos adversos , Sulbactam/farmacocinética , Resultado do Tratamento
2.
Chem Pharm Bull (Tokyo) ; 68(8): 806-809, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32461519

RESUMO

The direct electron transfer between human cytoglobin (Cygb) and the electrode surface, which would allow manipulating the oxidation states of the heme iron in Cygb, was first observed by immobilizing Cygb on a nanoporous gold (NPG) electrode via a carboxy-terminated alkanethiol. The voltammetric performances of the wild type and mutated Cygb-immobilized NPG electrodes were evaluated in the absence or presence of potential substrates. The obtained results demonstrated that the usefulness of the proposed method in understanding the function of Cygb in molecular basis.


Assuntos
Citoglobina/química , Técnicas Eletroquímicas/métodos , Citoglobina/genética , Citoglobina/metabolismo , Eletrodos , Transporte de Elétrons , Ouro/química , Humanos , Peróxido de Hidrogênio/química , Cinética , Mutagênese Sítio-Dirigida , Nanoporos , Oxirredução , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação
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