Monday, 30 November 2020

Potential Drugs for Treating COVID-19 Infection

 

The novel Coronavirus Disease 2019 (COVID-19) appeared as an emerging respiratory disease in December 2019 in Wuhan, Hubei province, China, and then spread rapidly worldwide, being declared a pandemic on March 11, 2020. Researchers are attempting to discover specifically designed antiviral treatments for COVID-19. Several therapeutic agents such as Interferon-α, Lopinavir/Ritonavir, Ribavirin, Chloroquine, Chloroquine phosphate, Hydroxychloroquine, Arbidol, Favipiravir, Remdesivir, Darunavir, Imatinib, Teicoplanin, Azithromycin, COVID-19 convalescent plasma, other potential antiviral drugs, and Chinese herbal agents are now being clinically studied to examine both pharmaceutical efficacy and safety for COVID-19 treatment in several countries. Some favorable results from these studies have been obtained to date. This review article summarizes and reiterates drugs that are potentially efficient against COVID-19.

Tim Sandle has contributed to a new peer reviewed research paper:

Mohammadi M, Sandle T , Rajabi S, Khorshidi A, Piroozmand A. Potential Drugs for Treating COVID-19 Infection, Int J Infect. 7 (4) :e106243. doi: 10.5812/iji.106243

Scientists are endeavouring to find drugs to treat COVID-19. These attempts are currently focused on at least 30 drugs such as natural agents, Western drugs, and traditional Chinese therapeutic agents, each of which is potentially efficient against COVID-19. Clinical studies have been rapidly conducted on some of these agents, and the results are indicative of their initial efficacy against COVID-19.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Sunday, 29 November 2020

Microbial growth and the relationship with culture media

 


In order to grow and reproduce microorganisms require biochemical factors - nutrients and a source of energy  - and certain biophysical factors - ambient conditions relating to pH, atmosphere and temperature. Take, for example, the nutritional requirements of the bacterium Escherichia coli. The nutrients this organism requires  are shown through the bacterial cell's elemental composition. Such elements are found in the form of water, inorganic ions, small molecules, and macromolecules which serve either a structural or functional role in the cells. For E. coli the major elements consist of those illustrated in Table 1.

 

Table 1:          Nutrient requirements for E. coli       

 

 

Element

Percentage of dry weight

Source

Cellular function

Carbon

50

Organic compounds or CO2

Main constituent of cellular material





Oxygen

20

H2O, organic compounds, CO2, and O2

Constituent of cell material and cell water; O2 is electron acceptor in aerobic respiration

Nitrogen

14

NH3, NO3, organic compounds, N2

Constituent of amino acids, nucleic acids nucleotides, and coenzymes

Hydrogen

8

H2O, organic compounds, H2

Main constituent of organic compounds and cell water

Phosphorus

3

inorganic phosphates (PO4)

Constituent of nucleic acids, nucleotides, phospholipids, LPS, teichoic acids

Sulfur

1

SO4, H2S, So, organic sulfur compounds

Constituent of cysteine, methionine, glutathione, several coenzymes

Potassium

1

Potassium salts

Main cellular inorganic cation and cofactor for certain enzymes

Magnesium

0.5

Magnesium salts

Inorganic cellular cation, cofactor for certain enzymatic reactions

Calcium

0.5

Calcium salts

Inorganic cellular cation, cofactor for certain enzymes and a component of endospores

Iron

0.2

Iron salts

Component of cytochromes and certain nonheme iron-proteins and a cofactor for some enzymatic reactions

 

In addition to the elements described in Table 1, E. coli cells also require trace elements in order to grow. These are elements like zinc, cobalt, and copper. Importantly, when discussing culture media, the main elements are used to help define what the culture medium should contain (even if the precise quantities are undefined; the differences between defined and undefined media are discussed below). With common media, the  exact quantities and proportions of trace elements are invariably unknown; therefore they are typically not added to culture media. Trace elements are often present as impurities in the water or other media components used in the culture media formulation.

 

In the environment (what might be assumed as the 'natural state'), microorganisms have adapted to the habitats most suitable to their needs. To replicate these conditions in the laboratory, such requirements are met by the use of culture media (which can be thought of as aqueous solutions containing the necessary nutrients to promote microbial growth). The range of nutritional and physical requirements for microbial growth include:

 

• Water,

• A source of energy,

• Sources of carbon (such as glucose), nitrogen (and amino acids), sulfur and phosphorus,

• Minerals and metals,

• Buffer salts,

• Vitamins and other growth factors.

 

It is these factors that culture media and incubation conditions attempt to reproduce. 

 Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Saturday, 28 November 2020

FDA new guidance: Physiologically based pharmacokinetic analyses


 

A new FDA draft guidance has been issued: ‘The use of physiologically based pharmacokinetic analyses — biopharmaceutics applications for oral drug product development, manufacturing changes, and controls’.

 

This guidance provides general recommendations regarding the development, evaluation, and use of physiologically based pharmacokinetic (PBPK) analyses for biopharmaceutics applications employed by sponsors of investigational new drug applications, and applicants for new drug applications, or abbreviated new drug applications, and supplements to these applications, for oral drug product development, manufacturing changes, and controls. 

 

 

PBPK analyses use models and simulations that combine physiology, population, and drug substance and product characteristics to mechanistically describe the pharmacokinetic (PK) and/or pharmacodynamic behaviors of a drug product. Although the pharmaceutical industry has in some cases been successful in developing in vitro/in vivo correlations (IVIVCs) to support biowaiver requests in lieu of in vivo BE studies for major manufacturing changes, development of an adequate IVIVC for regulatory submission remains challenging. FDA recognizes this challenge and encourages the development and use of new tools and approaches for linking pharmaceutical quality to clinical performance.

 

Advances in modelling and simulation have enabled the integration of factors such as the physicochemical properties of the active pharmaceutical ingredient (API), dissolution data, and the physiology of the GI tract into the development of PBPK models. As such, PBPK modeling has become a promising tool in predicting systemic drug exposure  and has been used for dose selection, food effect assessment, and drug interaction potential evaluation.

 

For details, see: https://www.fda.gov/media/142500/download

 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Special offers