Pafuramidine

Pafuramidine

Pafuramidine (also known as DB289 and DB75) is a synthetic, orally-active prodrug of Furamidine. It was developed by Immtech Pharmaceuticals and was in Phase III clinical trials for the treatment of Human African trypanosomiasis, also known as sleeping sickness, and Pneumocystis pneumonia (PCP) in patients with HIV/AIDS. However, the development was halted due to safety concerns.

Chemistry

Pafuramidine is a diamidine compound, specifically a prodrug of Furamidine. It is designed to improve the bioavailability and reduce the toxicity of the parent drug. The conversion of Pafuramidine to Furamidine occurs in the liver.

Pharmacology

Pafuramidine exhibits its activity by being metabolized to its active form, Furamidine. Furamidine then interferes with the DNA of the parasite, leading to its death. It is active against both the early (hemolymphatic) and late (neurological) stages of Human African trypanosomiasis.

Clinical Trials

Pafuramidine was in Phase III clinical trials for the treatment of Human African trypanosomiasis and Pneumocystis pneumonia in patients with HIV/AIDS. However, the trials were halted due to safety concerns, specifically potential kidney toxicity.

Safety

During the clinical trials, some patients developed kidney toxicity, which led to the halting of the trials. The exact cause of this toxicity is not known, but it is believed to be related to the metabolism of Pafuramidine in the body.

See Also

• Furamidine
• Prodrug
• Human African trypanosomiasis
• Pneumocystis pneumonia
• HIV/AIDS