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1.
Viruses ; 15(8)2023 08 14.
Article in English | MEDLINE | ID: mdl-37632075

ABSTRACT

We recently reported the isolation and characterization of an anti-SARS-CoV-2 antibody, called IgG-A7, that protects transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from an infection with SARS-CoV-2 Wuhan. We show here that IgG-A7 protected 100% of the transgenic mice infected with Delta (B.1.617.2) and Omicron (B.1.1.529) at doses of 0.5 and 5 mg/kg, respectively. In addition, we studied the pharmacokinetic (PK) profile and toxicology (Tox) of IgG-A7 in CD-1 mice at single doses of 100 and 200 mg/kg. The PK parameters at these high doses were proportional to the doses, with serum half-life of ~10.5 days. IgG-A7 was well tolerated with no signs of toxicity in urine and blood samples, nor in histopathology analyses. Tissue cross-reactivity (TCR) with a panel of mouse and human tissues showed no evidence of IgG-A7 interaction with the tissues of these species, supporting the PK/Tox results and suggesting that, while IgG-A7 has a broad efficacy profile, it is not toxic in humans. Thus, the information generated in the CD-1 mice as a PK/Tox model complemented with the mouse and human TCR, could be of relevance as an alternative to Non-Human Primates (NHPs) in rapidly emerging viral diseases and/or quickly evolving viruses such as SARS-CoV-2.


Subject(s)
COVID-19 , Animals , Mice , SARS-CoV-2 , Antibodies, Viral , Mice, Transgenic , Antibodies, Neutralizing , Immunoglobulin G , Receptors, Antigen, T-Cell
2.
Bioanalysis ; 9(6): 569-579, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28225297

ABSTRACT

AIM: Cinitapride (CIN) is a benzamide-derived molecule used for the treatment of gastroesophageal reflux and dyspepsia. Its pharmacokinetics are controversial due to the use of supratherapeutic doses and the lack of sensitive methodology. Therefore, a sensitive and accurate micromethod was developed for its quantitation in human plasma. RESULTS: CIN was extracted from 300 µl of heparinized plasma by liquid-liquid extraction using cisapride as internal standard, and analyzed with an ultra performance liquid chromatograph employing positive multiple-reaction monitoring-MS. CONCLUSION: The method proved to be rapid, accurate and stable within a range between 50 and 2000 pg/ml and was successfully validated and applied in a pharmacokinetic interaction trial, where it was demonstrated that oral co-administration of simethicone does not modify the bioavailability of CIN.


Subject(s)
Benzamides/blood , Chromatography, High Pressure Liquid/methods , Spectrometry, Mass, Electrospray Ionization/methods , Tandem Mass Spectrometry/methods , Administration, Oral , Adolescent , Adult , Area Under Curve , Benzamides/administration & dosage , Benzamides/pharmacokinetics , Calibration , Chromatography, High Pressure Liquid/instrumentation , Cross-Over Studies , Healthy Volunteers , Humans , Limit of Detection , Liquid-Liquid Extraction , Middle Aged , Reference Standards , Sensitivity and Specificity , Spectrometry, Mass, Electrospray Ionization/instrumentation , Tandem Mass Spectrometry/instrumentation , Young Adult
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