paromomycin

paromomycin
IUPAC name	(2R,3S,4R,5R,6S)-5-amino-6-[(1R,2S,3S,4R,6S)-4,6-diamino-2-[(2S,3R,4S,5R)-4-[(2R,3R,4R,5R,6S)-3-amino-6-(aminomethyl)-4,5-dihydroxyoxan-2-yl]oxy-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-3-hydroxycyclohexyl]oxy-2-(hydroxymethyl)oxane-3,4-diol
Width	200
Tradename	Humatin, others
Drugs.com	monograph, paromomycin
Routes of administration	Oral, intramuscular (limited)
CAS number	7542-37-2
PubChem	165580
ChemSpiderID	145108
UNII	4Z8P6C6E2M
ChEBI	28260
ChEMBL	1743009
ATC prefix	A07
ATC suffix	AA06
Legal AU	S4
Legal UK	POM
Legal US	Rx-only

paromomycin is an aminoglycoside antibiotic derived from the bacterium Streptomyces rimosus var. *paromomycinus*. It is primarily used as an oral agent for the treatment of intestinal amebiasis and hepatic encephalopathy, and is a critical component in the management of certain neglected tropical diseases, notably visceral leishmaniasis. Its development and application are closely associated with research from institutions like the World Health Organization and the Centers for Disease Control and Prevention.

Medical uses

It is indicated for the treatment of amebic dysentery and amebic liver abscess caused by Entamoeba histolytica, often in combination with other agents like metronidazole. It serves as a second-line therapy for cryptosporidiosis in patients with HIV/AIDS, as recognized by the U.S. Food and Drug Administration. A significant modern use is as an intramuscular injection for visceral leishmaniasis (kala-azar), particularly in regions like East Africa and the Indian subcontinent, following protocols established by the World Health Organization. It is also used for preoperative suppression of intestinal flora and in the management of hepatic encephalopathy to reduce ammonia-producing bacteria.

Mechanism of action

As an aminoglycoside, it binds irreversibly to the bacterial 30S ribosomal subunit, specifically to the 16S rRNA component within the A-site of the ribosome. This binding interferes with the initiation complex during protein synthesis and induces misreading of the mRNA template, leading to the incorporation of incorrect amino acids and the production of nonfunctional or toxic peptides. This action is bactericidal against susceptible enteric pathogens. For Leishmania parasites, the mechanism may involve disruption of mitochondrial function and inhibition of protein synthesis within the kinetoplast.

Adverse effects

Common adverse effects from oral administration are largely confined to the gastrointestinal tract and include nausea, abdominal cramps, and diarrhea. Intramuscular administration, used for visceral leishmaniasis, carries risks typical of systemic aminoglycosides, such as ototoxicity (affecting both auditory and vestibular functions) and nephrotoxicity. Other potential effects include skin rash and vertigo. Its use is contraindicated in patients with intestinal obstruction or myasthenia gravis, and it carries a Pregnancy Category D rating due to potential fetal harm.

Pharmacokinetics

It is poorly absorbed from the gastrointestinal tract, with over 99% of an oral dose remaining within the intestinal lumen, which is the basis for its use against enteric infections. Systemic absorption is minimal but can increase with conditions like ulcerative colitis. When administered intramuscularly, it is well absorbed, achieving peak serum concentrations within one hour. It is excreted largely unchanged in the feces following oral use, and via glomerular filtration in the kidneys after parenteral administration. It does not undergo significant hepatic metabolism.

History

It was first isolated in the 1950s from a strain of Streptomyces rimosus by researchers at Parke-Davis, following the era of discovery initiated by Selman Waksman with streptomycin. Its initial applications were for amebiasis and as a broad-spectrum antibacterial. Its potential against visceral leishmaniasis was explored later, with pivotal clinical trials conducted in the 1990s in India and Africa, leading to its inclusion in the World Health Organization's Essential Medicines List. Its manufacturing and distribution for neglected diseases have involved partnerships with organizations like the Drugs for Neglected Diseases initiative.

Society and culture

It is on the World Health Organization's List of Essential Medicines and is marketed under brand names including Humatin. Its role in combating visceral leishmaniasis, a disease of poverty, highlights issues of global health equity and access to medicines. Production and supply are often managed through international programs supported by entities like the World Health Organization and the Bill & Melinda Gates Foundation. The drug's use is a component of public health strategies in endemic countries such as Bangladesh, India, Sudan, and Ethiopia.

Category:Aminoglycoside antibiotics Category:World Health Organization essential medicines Category:Antiprotozoal agents