RESUMO
Insulin aspart (IAsp) is one of the main therapies used to control blood glucose after a meal. This study aimed to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of 2 rapid-acting IAsp products: a new IAsp biosimilar (RD10046) and NovoRapid. In a single-center, randomized, single-dose, 2-period, crossover, euglycemic clamp study (registry number: CTR20180517, registration date: 2018-05-30), healthy Chinese males were randomized to receive 0.2 U/kg of the IAsp biosimilar RD10046 and NovoRapid under fasted conditions on two separate occasions. PK and PD were assessed for up to 10 h. Of the 30 randomized subjects, all 30 completed both treatment periods. The PK (area under the curve [AUC] of total IAsp; maximum observed IAsp concentration [Cmax]) and PD (maximum glucose infusion rate [GIRmax]; total glucose infusion during the clamp [AUCGIR,0-10h]) were similar between the new IAsp biosimilar RD10046 and NovoRapid. In all cases, the 90% CIs for the ratios of the geometric means were completely contained in the prespecified acceptance limits of 0.80-1.25. No hypoglycemic events, allergic reactions, or local injection adverse reactions occurred in this trial. We concluded that the studied IAsp biosimilar (RD10046) was bioequivalent to NovoRapid.
Assuntos
Medicamentos Biossimilares/farmacocinética , Medicamentos Biossimilares/uso terapêutico , Insulina Aspart/farmacocinética , Insulina Aspart/uso terapêutico , Adulto , Povo Asiático , Glicemia/efeitos dos fármacos , Estudos Cross-Over , Combinação de Medicamentos , Técnica Clamp de Glucose/métodos , Humanos , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Insulina de Ação Prolongada/farmacocinética , Insulina de Ação Prolongada/uso terapêutico , Masculino , Adulto JovemRESUMO
Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. In a previous study we reported the synthesis of a series of apocynin derivatives. Although the anti-inflammatory activity of them contributes to these cytoprotective effects. However, the mechanisms and effects of improving LPS-induced ALI in vivo remain unknown, so the purpose of our investigation was designed to reveal the effect of apocynin derivatives on LPS-induced acute lung injury in rats. The present study showed that apocynin derivatives reduces overall protein levels and tumor necrosis factor α (TNF-α) level, inhibits the activation of NADPH oxidase, and increases the levels of superoxide dismutase (SOD). Especially, compound 11 significantly reduces pulmonary vascular permeability, white blood cell content and protein expressions of p67(phox) and p47(phox). These results suggest that compound 11 can ameliorate ALI induced by LPS through inhibition of NADPH oxidase.
Assuntos
Acetofenonas/administração & dosagem , Lesão Pulmonar Aguda/tratamento farmacológico , Misturas Complexas/administração & dosagem , Leucócitos/efeitos dos fármacos , Óxidos de Nitrogênio/administração & dosagem , Acetofenonas/química , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Permeabilidade Capilar/efeitos dos fármacos , Humanos , Leucócitos/patologia , Lipopolissacarídeos/imunologia , Masculino , NADPH Oxidases/metabolismo , Fosfoproteínas/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
We have designed and synthesized a series of novel apocynin analogues, and evaluated their biological activity. Compound 10, an apocynin dimer analogue, compound 12, the lipoic acid (LA) and apocynin conjugate, were the most potent in protecting cells from lipopolysaccharide (LPS)-induced cytotoxicity, had significant activity scavenging ROS induced by LPS, and greatly decreased LPS-induced P67(phox) protein expression. SAR analysis suggests that modification of apocynin can increase its activity. Our results demonstrate that arming apocynin with a powerful antioxidant such as lipoic acid is a valid strategy to design new apocynin analogues with enhanced biological activity.
