Repurposed Pyrazinamide Delivers Drug Through the Lungs for Tuberculosis

Pyrazinoic acid repurposed to deliver drug into the lungs vs oral administration shows new hope for tuberculosis treatment

Highlights:

Tuberculosis caused by bacteria affect lungs and other organs in the body.
Administering drug via the lungs vs oral administration shows new hope in the treatment of tuberculosis.
Pyrazinoic acid that has been repurposed to deliver the drug into the lungs was found to show promising results.

Administering drug to treat tuberculosis through the lungs as opposed to oral administration shows promise, demonstrates a study presented at the American Association of Pharmaceutical Scientists(AAPS) Annual Meeting and Exposition.//

More than 1.8 million deaths each year occur due to tuberculosis according to the World Health Organization. Tuberculosis caused by the Mycobacterium tuberculosis bacteria not only affect the lungs but also affect other organs like lymph nodes and spleen.

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Tuberculosis, caused by Mycobacterium tuberculosis, primarily affects the lung. It may spread to other organs.

‘Administering repurposed drug via the lungs for tuberculosis shows promising treatment results.’

Repurposed drug to treat tuberculosis when administered via the lungs were found to be effective at a fraction of dose which is 10 times less than the oral administration.

The research study also found the new treatment to be beneficial in reducing toxicity to the body and other organs.

Pyrazinamide (PZA) , a first line agent for tuberculosis treatment was administered orally. It was found to act as a prodrug which gets converted into the active moiety pyrazinoic acid (POA) by microbial enzymatic action.

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Pyrazinamide resistance occurs due to the mutation of the enzyme which is responsible for converting pyrazinamide to pyrazinoic acid.

Oral pyrazinoic acid is not effective for treatment and delivering pyrazinoic acid along with its non hydrolysable ester, n-propyl POA (PAE) can provide mitigating resistance for the active moiety.

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Administering the drug to the lungs require less amount of the drug to reduce burden in the lungs which is a major site of infection and transmission for tuberculosis.

Phillip Durham, biochemist at RTI International in Raleigh - Durham, N.C. said, "When it comes to TB therapy, there have not been a lot of new drugs introduced to market during the past two decades, and progress is slow despite enormous effort in new drug discovery."

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"What we've done in our research, "is to use a derivative of a drug that has been around for many years -- Pyrazinoic acid -- and repurposed the drug to deliver it to the lungs, with some very promising results." he added.

The research study also demonstrated that aerosol administration to the lungs were effective when compared to high dose of oral pyrazinamide in the spleen.

Oral pyrazinamide drug was found to produce toxic side effects, reducing the dose while producing same efficacy levels to help patients.

The author says, "For drugs that are not orally bioavailable, the alternative is often injection," "Given the dose required, daily therapy, and the physical health of the patients, inhaled therapy has the potential to be far less painful, does not generate biohazardous waste like HIV contaminated needles (HIV/TB coinfection is a problem), and does not need to be kept cold, which is required by many injectables."

Source-Medindia