Review of commonly used age based weight estimates for paediatric drug dosing in relation to the pharmacokinetic properties of resuscitation drugs

SummaryIn an effort to modify the fibrinolytic and/or pharmacokinetic properties of recombinant low M r single-chain urokinase-type plasminogen activator (rscu-PA-32k), mutants were prepared by site-directed mutagenesis of clusters of charged amino acids with the highest solvent accessibility. The following mutants of rscu-PA-32k were prepared: LUK-2 (Lys 212, Glu 213 and Asp 214 to Ala), LUK-3 (Lys 243 and Asp 244 to Ala), LUK-4 (Arg 262, Lys 264, Glu 265 and Arg 267 to Ala), LUK-5 (Lys 300, Glu 301 and Asp 305 to Ala) and LUK-6 (Arg 400, Lys 404, Glu 405 and Glu 406 to Ala).The rscu-PA 32k moictic3 were expressed in High Five Ttichoplasiani cells, and purified to humugciicily from the conditioned cell culture medium, with recoveries of 0.8 to 3.7 mg/1. The specific fibrinolytic activities (220,000 to 300,000 IU/mg), the rates of plasminogen activation by the single-chain moieties and the rates of conversion In lwo chain moieties by plasmin were comparable for mutant and wild-type rscu PA 32k moieties, with the exception of LUK-5 which was virtually inactive. Equi-effective lysis (50% in 2 h) of 60 pi 125I-fibrin labeled plasma clots submerged in 0.5 ml normal human plasma was obtained with 0.7 to 0.8 μg/ml of wild-type or mutant rscu-PA-3?.k, except with LUK-5 (no significant lysis with 16 pg/ml). Following bolus injection in hamsters, all rscu-PA-32k moieties had a comparably rapid plasma clearance (1.3 to 2.7 ml/min), as a result of a short initial half-life (1.4 to 2.5 min). In hamsters with pulmonary embolism, continuous intravenous infusion over 60 min at a dose of 1 mg/kg, resulted in 53 to 72% clot lysis with the mutants, but only 23% with LUK-5, as compared to 36% for wild-type rscu-PA-32k.These data indicate that clustered charge-to-alanine mutants of rscu-PA-32k, designed to eliminate charged regions with the highest solvent accessibility, do not have significantly improved functional, fibrinolytic or pharmacokinetic properties.

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A Peptoid with Extended Shape in Water

10.26434/chemrxiv.7552139 ◽

2019 ◽

Author(s):

Jumpei Morimoto ◽

Yasuhiro Fukuda ◽

Takumu Watanabe ◽

Daisuke Kuroda ◽

Kouhei Tsumoto ◽

...

Keyword(s):

Spectroscopic Analysis ◽

Dimensional Space ◽

Three Dimensional ◽

Biomolecular Recognition ◽

Biological Application ◽

New Class ◽

Proteolytic Resistance ◽

Pharmacokinetic Properties ◽

Optically Pure ◽

Three Dimensional Space

<div> <div> <div> <p>“Peptoids” was proposed, over decades ago, as a term describing analogs of peptides that exhibit better physicochemical and pharmacokinetic properties than peptides. Oligo-(N-substituted glycines) (oligo-NSG) was previously proposed as a peptoid due to its high proteolytic resistance and membrane permeability. However, oligo-NSG is conformationally flexible and is difficult to achieve a defined shape in water. This conformational flexibility is severely limiting biological application of oligo-NSG. Here, we propose oligo-(N-substituted alanines) (oligo-NSA) as a new peptoid that forms a defined shape in water. A synthetic method established in this study enabled the first isolation and conformational study of optically pure oligo-NSA. Computational simulations, crystallographic studies and spectroscopic analysis demonstrated the well-defined extended shape of oligo-NSA realized by backbone steric effects. The new class of peptoid achieves the constrained conformation without any assistance of N-substituents and serves as an ideal scaffold for displaying functional groups in well-defined three-dimensional space, which leads to effective biomolecular recognition. </p> </div> </div> </div>

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Double-Crosslinked Nanocomposite Hydrogels for Temporal Control of Drug Dosing in Combination Therapy

SSRN Electronic Journal ◽

10.2139/ssrn.3454944 ◽

2019 ◽

Author(s):

Can Wu ◽

Jing Liu ◽

Ziran Zhai ◽

Xuan Tang ◽

Keming Xu ◽

...

Keyword(s):

Combination Therapy ◽

Temporal Control ◽

Drug Dosing ◽

Nanocomposite Hydrogels

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Targeting COVID-19 in Parkinson’s patients: Drugs repurposed.

Current Medicinal Chemistry ◽

10.2174/0929867327666200903115138 ◽

2020 ◽

Vol 27 ◽

Author(s):

Firoz Anwar ◽

Salma Naqvi ◽

Fahad A. Al-Abbasi ◽

Nauroz Neelofar ◽

Vikas Kumar ◽

...

Keyword(s):

Day Treatment ◽

Treatment Options ◽

Developed Countries ◽

Methyl Transferase ◽

Comt Inhibitors ◽

Mao B ◽

Pharmacokinetic Properties ◽

Us Fda ◽

Approved Drugs ◽

Fda Approved Drugs

: The last couple of months have witnessed the world in a state of virtual standstill. The SARS-CoV-2 virus has overtaken globe to economic and social lockdown. Many patients with COVID-19 have compromised immunity, especially in an aged population suffering from Parkinson disease (PD). Alteration in dopaminergic neurons or deficiency of dopamine in PD patients is the most common symptoms affecting 1% population above the age of 60 years. The compromised immune system and inflammatory manifestation in PD patients make them an easy target. The most common under trial drugs for COVID-19 are Remdesivir, Favipiravir, Chloroquine and Hydroxychloroquine, Azithromycin along with adjunct drugs like Amantadine with some monoclonal antibodies. : Presently, clinically US FDA approved drugs in PD includes Levodopa, catechol-O-methyl transferase (COMT) inhibitors, (Entacapone and Tolcapone), Dopamine agonists (Bromocriptine, Ropinirole, Pramipexole, and Rotigotine), Monoamine oxidase B (MAO-B) inhibitors (Selegiline and Rasagiline), Amantadine and Antimuscarinic drugs. The drugs have established mechanism of action on PD patients with known pharmacodynamics and pharmacokinetic properties along with dose and adverse effects. : Conclusion and relevance of this review focus on the drugs that can be tried for the PD patients with SAR CoV-2 infection, in particular, Amantadine approved by all developed countries a common drug possessing both antiviral properties by downregulation of CTSL, lysosomal pathway disturbance and change in pH necessary to uncoat the viral proteins and antiParkinson properties. The significant prognostic adverse effect of SARS-CoV-2 on PD and the present-day treatment options, clinical presentation and various mechanism is warrant need of the hour.

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A Comprehensive Insight Towards Pharmaceutical Aspects of Graphene Nanosheets

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200318131422 ◽

2020 ◽

Vol 21 (11) ◽

pp. 1016-1027 ◽

Cited By ~ 2

Author(s):

Fatemeh Emadi ◽

Arash Emadi ◽

Ahmad Gholami

Keyword(s):

Targeted Delivery ◽

Graphene Nanosheets ◽

High Surface ◽

High Surface Area ◽

Charge Carriers ◽

Pharmaceutical Sciences ◽

Pharmacokinetics And Pharmacodynamics ◽

Mobility Of Charge Carriers ◽

Graphene Derivatives ◽

Pharmacokinetic Properties

Graphene Derivatives (GDs) have captured the interest and imagination of pharmaceutical scientists. This review exclusively provides pharmacokinetics and pharmacodynamics information with a particular focus on biopharmaceuticals. GDs can be used as multipurpose pharmaceutical delivery systems due to their ultra-high surface area, flexibility, and fast mobility of charge carriers. Improved effects, targeted delivery to tissues, controlled release profiles, visualization of biodistribution and clearance, and overcoming drug resistance are examples of the benefits of GDs. This review focuses on the application of GDs for the delivery of biopharmaceuticals. Also, the pharmacokinetic properties and the advantage of using GDs in pharmaceutics will be reviewed to achieve a comprehensive understanding about the GDs in pharmaceutical sciences.

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