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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H24N4O2.2C6H12O7
Molecular Weight 732.73
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PENTAMIDINE GLUCONATE

SMILES

OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.NC(=N)C1=CC=C(OCCCCCOC2=CC=C(C=C2)C(N)=N)C=C1

InChI

InChIKey=JAVCHNFPSHBZAF-UUPCJSQJSA-N
InChI=1S/C19H24N4O2.2C6H12O7/c20-18(21)14-4-8-16(9-5-14)24-12-2-1-3-13-25-17-10-6-15(7-11-17)19(22)23;2*7-1-2(8)3(9)4(10)5(11)6(12)13/h4-11H,1-3,12-13H2,(H3,20,21)(H3,22,23);2*2-5,7-11H,1H2,(H,12,13)/t;2*2-,3-,4+,5-/m.11/s1

HIDE SMILES / InChI

Description

Pentamidine (formulated as a salt, pentamidine diisethionate or dimesilate) is an antimicrobial medication given for prevention and treatment of pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii (formerly known as Pneumocystis carinii), a severe interstitial type of pneumonia often seen in patients with HIV infection. The drug is also the mainstay of treatment for stage I infection with Trypanosoma bruceigambiense (West African trypanosomiasis). Pentamidine is also used as a prophylactic against PCP in patients receiving chemotherapy and in some patients who have undergone organ transplantation, as they also have a depressed immune system as a direct side-effect of the drugs used. The mortality of untreated PCP is very high. Additionally, pentamidine has good clinical activity in treating leishmaniasis, and yeast infections caused by the organism Candida albicans. Pentamidine is also used as a prophylactic antibiotic for children undergoing treatment for leukemia. Studies suggest that the pentamidine isethionate interferes with microbial nuclear metabolism by inhibition of DNA, RNA, phospholipid and protein synthesis. However, the mode of action is not fully understood.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
204.4 µM [EC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
NEBUPENT

Cmax

ValueDoseCo-administeredAnalytePopulation
751 nM
3.9 mg/kg 1 times / day multiple, intravenous
PENTAMIDINE blood
Homo sapiens
612 ng/mL
4 mg/kg single, intravenous
PENTAMIDINE plasma
Homo sapiens
18.8 ng/mL
4 mg/kg 1 times / day multiple, irrigation
PENTAMIDINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
6734 nM × h
3.9 mg/kg 1 times / day multiple, intravenous
PENTAMIDINE blood
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
6.4 h
4 mg/kg single, intravenous
PENTAMIDINE plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
The recommended adult dosage is 300 mg once every four weeks administered via the Respirgard® II nebulizer. The dose should be delivered until the nebulizer chamber is empty (approximately 30 to 45 minutes). The flow rate should be 5 to 7 liters per minute from a 40 to 50 pounds per square inch (PSI) air or oxygen source. Alternatively, a 40 to 50 PSI air compressor can be used with flow limited by setting the flowmeter at 5 to 7 liters per minute or by setting the pressure at 22 to 25 PSI. Low pressure (less than 20 PSI) compressors should not be used.
Route of Administration: Irrigation
In Vitro Use Guide
Pentamidine was found to be active against T. whipplei strains both in axenic medium and in cell culture, with minimum inhibitory concentration ranges of 0.125-0.25mg/L.