The fungal form of meningitis is rare and is usually caused by fungus spreading through blood to the spinal cord. It leads to more than 600,000 deaths in
Africa every year and is responsible for 20% of HIV/AIDS-related
deaths globally, suggests the U.S. Centers for Disease Control and
An existing medicine could help curb these numbers, but its cost has been a barrier to access in some places. Now, scientists report in the ACS journal Organic Process Research & Development a more affordable way to make the drug.
The antifungal flucytosine has been available to patients in the U.S. for decades. In 2011, the World Health Organization (WHO) recommended that patients with Cryptococcal meningitis, an infection of particular concern to people with HIV/AIDS, take flucytosine in combination with amphotericin B as a first line of defense.
To help slash flucytosine's price tag and improve its availability, Graham Sandford and colleagues at Durham University in the U.K. wanted to come up with a simpler, lower cost way to make the drug.
The researchers developed a one-step technique to make flucytosine out of readily available, naturally occurring cytosine. Their process involved simultaneously pumping inexpensive fluorine gas and a solution of cytosine in formic acid through a steel tube. This fluorinated all of the starting cytosine, and the researchers were able to isolate high yields of the resulting flucytosine by recrystallization.
The researchers say the method should be simple to scale up for manufacturing and could help lower the drug's cost. The one-step method has been successfully developed to pilot-scale by industrial collaborators Sanofi-Aventis and La Maison Européenne des Procédés Innovants in France.