Synopsis
Synopsis
0
API Suppliers
0
USDMF
0
CEP/COS
0
JDMF
0
EU WC
0
KDMF
0
NDC API
0
VMF
0
Listed Suppliers
0
FDA Orange Book
0
Canada
0
Australia
0
South Africa
0
Listed Dossiers
DRUG PRODUCT COMPOSITIONS
0
EDQM
0
USP
0
JP
0
Others
0
US Patents
0
US Exclusivities
0
Health Canada Patents
0
Data Compilation #PharmaFlow
0
Stock Recap #PipelineProspector
0
Weekly News Recap #Phispers
1. Diamidine
2. Lomidine
3. Nebupent
4. Pentacarinat
5. Pentam
6. Pentamidin
7. Pentamidine Isethionate
8. Pentamidine Mesylate
1. 100-33-4
2. 4,4'-(pentane-1,5-diylbis(oxy))dibenzimidamide
3. Pentamide
4. 4,4'-diamidinodiphenoxypentane
5. Pentam 300
6. P,p'-(pentamethylenedioxy)dibenzamidine
7. 4,4'-(pentamethylenedioxy)dibenzamidine
8. 4-[5-(4-carbamimidoylphenoxy)pentoxy]benzenecarboximidamide
9. Pentamidine (inn)
10. Pentamidin
11. 1,5-bis(4-amidinophenoxy)pentane
12. 4,4'-(1,5-pentanediylbis(oxy))bis-benzenecarboximidamide
13. Nsc-9921
14. Mb-800
15. Pnt
16. 4-{[5-(4-carbamimidoylphenoxy)pentyl]oxy}benzene-1-carboximidamide
17. Rp-2512
18. Mb 800 Free Base
19. Mb-800 Free Base
20. Gnf-pf-3680
21. Rp 2512 Free Base
22. Rp-2512 Free Base
23. 4,4'-[pentane-1,5-diylbis(oxy)]dibenzenecarboximidamide
24. 673lc5j4lq
25. Benzenecarboximidamide, 4,4'-(1,5-pentanediylbis(oxy))bis-
26. Benzenecarboximidamide, 4,4'-[1,5-pentanediylbis(oxy)]bis-
27. Pentamidina
28. Pentamidinum
29. Chebi:45081
30. Nsc9921
31. Mb 800 [as Isethionate]
32. Mb-800 (as Isethionate)
33. 4,4'-[1,5-pentanediylbis(oxy)]bis-benzenecarboximidamide
34. Pentamidina [dcit]
35. Mp-601205
36. Pentamidine [inn]
37. Pentam 300 (as Isethionate)
38. Nebupent (as Isethionate)
39. Pentamidinum [inn-latin]
40. Rp 2512 [as Isethionate]
41. Pentacarinat (as Isethionate)
42. Pentamidine [inn:ban:dcf]
43. Rp 2512 [as Isethionate)
44. Lomidine (tn)
45. 4,4'-(pentamethylenedioxy)dibenzamidine;4,4'-(pentane-1,5-diylbis(oxy))dibenzimidamide;4-{[5-(4-carbamimidoylphenoxy)pentyl]oxy}benzene-1-carboximidamide
46. Ccris 3825
47. Nsc620107
48. 4, 4'-diamidinodiphenoxypentane
49. 1,3-bis(4-amidinophenoxy)pentane
50. P,p'-(pentamethylene-dioxy)bis-benzamidine
51. Nebupent (*isethionate)
52. Nsc 9921
53. Einecs 202-841-0
54. Pentacarinat (*isethionate)
55. Brn 3159790
56. Unii-673lc5j4lq
57. Pentam 300 (*isethionate)
58. Rp 2512 (*isethionate)
59. Hsdb 7474
60. 4,4'-(pentamethylenedioxy)dibenzamide
61. 4-[5-(4-carbamimidoylphenoxy)pentoxy]benzenecarboximidamide;2-hydroxyethanesulfonic Acid
62. P,p'-(pentamethylenedioxy)bis[benzamidine]
63. Chembl55
64. Pentamidine [mi]
65. Benzamidine, 4,4'-(pentamethylenedioxy)di-
66. Prestwick1_000553
67. Prestwick2_000553
68. Prestwick3_000553
69. Spectrum2_000155
70. Spectrum3_000276
71. Spectrum4_000380
72. Spectrum5_001808
73. Pentamidine [hsdb]
74. 4,.omega.-diphenoxypentane
75. Pentamidine [vandf]
76. Schembl3329
77. 4-[5-(4-carbamimidoylphenoxy)pentoxy]benzamidine
78. Bspbio_000625
79. Bspbio_001752
80. Kbiogr_000879
81. Pentamidine [who-dd]
82. 4-10-00-00447 (beilstein Handbook Reference)
83. Mls006011562
84. Spbio_000290
85. Spbio_002546
86. Bpbio1_000689
87. Cid_359323
88. Wln: Muyzr Do5or Dyzum
89. Dtxsid7023431
90. Bdbm45440
91. Kbio3_001252
92. Hms2089j14
93. Bcp10950
94. Hy-b0537
95. Zinc1530775
96. Mfcd00599574
97. Mmv000062
98. Pr-118
99. Akos015919681
100. Db00738
101. Ds-1680
102. Sdccgsbi-0050899.p002
103. Benzamidine,4'-(pentamethylenedioxy)di-
104. Ncgc00179034-01
105. Ncgc00179034-02
106. Ncgc00179034-03
107. Ncgc00179034-04
108. Ncgc00179034-08
109. Ncgc00179034-23
110. Ac-12459
111. Mp601205
112. Nci60_042221
113. Smr001549987
114. Sbi-0051570.p002
115. Ab00053572
116. Ft-0673594
117. C07420
118. D08333
119. Ab00053572-18
120. Ab00053572_19
121. Ab00053572_20
122. 100p334
123. Q416206
124. J-000106
125. Brd-k13183738-001-01-1
126. Brd-k13183738-317-06-0
127. Sr-01000075174-14
128. Benzenecarboximidamide,4'-[1,5-pentanediylbis(oxy)]bis-
129. 4-[5-(4-amidinophenoxy)pentoxy]benzamidine;2-hydroxyethanesulfonic Acid
130. 4-[5-(4-carbamimidoylphenoxy)pentoxy]benzenecarboximidamide;2-oxidanylethanesulfonic Acid
| Molecular Weight | 340.4 g/mol |
|---|---|
| Molecular Formula | C19H24N4O2 |
| XLogP3 | 2.6 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 10 |
| Exact Mass | 340.18992602 g/mol |
| Monoisotopic Mass | 340.18992602 g/mol |
| Topological Polar Surface Area | 118 Ų |
| Heavy Atom Count | 25 |
| Formal Charge | 0 |
| Complexity | 376 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Covalently Bonded Unit Count | 1 |
| 1 of 4 | |
|---|---|
| Drug Name | Nebupent |
| PubMed Health | Pentamidine |
| Drug Classes | Antiprotozoal |
| Drug Label | NebuPent (pentamidine isethionate), an antifungal agent, is a nonpyrogenic lyophilized product. After reconstitution with Sterile Water for Injection, USP, NebuPent is administered by inhalation via the Respirgard II nebulizer [Marquest, Englewood,... |
| Active Ingredient | Pentamidine isethionate |
| Dosage Form | For solution |
| Route | Inhalation |
| Strength | 300mg/vial |
| Market Status | Prescription |
| Company | Fresenius Kabi Usa |
| 2 of 4 | |
|---|---|
| Drug Name | Pentam |
| PubMed Health | Chloramphenicol (Into the eye) |
| Drug Classes | Antibiotic |
| Drug Label | Pentam 300 (pentamidine isethionate for injection), an anti-protozoal agent, is a sterile, nonpyrogenic, lyophilized product. After reconstitution, it should be administered by intramuscular (IM) or intravenous (IV) routes (see DOSAGE AND ADMINISTR... |
| Active Ingredient | Pentamidine isethionate |
| Dosage Form | Injectable |
| Route | Injection |
| Strength | 300mg/vial |
| Market Status | Prescription |
| Company | Fresenius Kabi Usa |
| 3 of 4 | |
|---|---|
| Drug Name | Nebupent |
| PubMed Health | Pentamidine |
| Drug Classes | Antiprotozoal |
| Drug Label | NebuPent (pentamidine isethionate), an antifungal agent, is a nonpyrogenic lyophilized product. After reconstitution with Sterile Water for Injection, USP, NebuPent is administered by inhalation via the Respirgard II nebulizer [Marquest, Englewood,... |
| Active Ingredient | Pentamidine isethionate |
| Dosage Form | For solution |
| Route | Inhalation |
| Strength | 300mg/vial |
| Market Status | Prescription |
| Company | Fresenius Kabi Usa |
| 4 of 4 | |
|---|---|
| Drug Name | Pentam |
| PubMed Health | Chloramphenicol (Into the eye) |
| Drug Classes | Antibiotic |
| Drug Label | Pentam 300 (pentamidine isethionate for injection), an anti-protozoal agent, is a sterile, nonpyrogenic, lyophilized product. After reconstitution, it should be administered by intramuscular (IM) or intravenous (IV) routes (see DOSAGE AND ADMINISTR... |
| Active Ingredient | Pentamidine isethionate |
| Dosage Form | Injectable |
| Route | Injection |
| Strength | 300mg/vial |
| Market Status | Prescription |
| Company | Fresenius Kabi Usa |
Pentamidine is indicated in the treatment of Pneumocystis carinii pneumonia (PCP) in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS). Sulfamethoxazole and trimethoprim combination is considered to be the primary agent for PCP in patients who can tolerate it. /Included in US product labeling/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007.
Pentamidine is used as a secondary agent in the treatment of visceral leishmaniasis (kala-azar) caused by Leishmania donovani. Stibogluconate sodium, a pentavalent antimony derivative, is considered to be the primary agent for visceral leishmaniasis. /NOT included in US product labeling/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007.
Pentamidine is used as a secondary agent in the treatment of cutaneous leishmaniasis caused by Leishmania tropica, L. major, L. mexicana, L. aethiopica, L. peruviana, L. guyanensis, and L. braziliensis. Stibogluconate sodium, a pentavalent antimony derivative, is considered to be the primary agent for cutaneous leishmaniasis. /NOT included in US product labeling/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007.
Aerosolized pentamidine is indicated in both secondary prophylaxis (patients who have already had at least one episode of Pneumocystis carinii pneumonia) and primary prophylaxis (HIV-infected patient with a CD4 lymphocyte count less than or equal to 200 cells per cubic millimeter) of Pneumocystis carinii pneumonia. /Included in US product labeling/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 2337
For more Therapeutic Uses (Complete) data for PENTAMIDINE (12 total), please visit the HSDB record page.
Fatalities due to severe hypotension, hypoglycemia, acute pancreatitis and cardiac arrhythmias have been reported in patients treated with pentamidine isethionate, both by the IM and IV routes. Severe hypotension may result after a single IM or IV dose and is more likely with rapid IV administration. The administration of the drug should, therefore, be limited to the patients in whom Pneumocystis carinii has been demonstrated. Patients should be closely monitored for the development of serious adverse reactions.
Prescribing Information for Pentam 300 (Pentamidine Isethionate for Injection); American Pharmaceutical Partners, Inc, Schaumburg, IL (2002). Available from, as of December 28, 2006: https://www.appdrugs.com/PIs/Pentam_300_45851A.pdf
Nephrotoxicity reportedly occurs in at least 25% of patients with pneumocystis pneumonia receiving parenteral pentamidine isethionate. Pentamidine-induced nephrotoxicity is manifested by an increase in serum creatinine concentration and/or BUN, usually developing gradually and appearing during the second week of therapy with the drug. Azotemia also has been reported. Renal insufficiency is usually mild to moderate in severity and reversible following discontinuance of pentamidine; however, acute renal failure (e.g., serum creatinine concentration greater than 6 mg/dL) or severe renal insufficiency requiring discontinuance of the drug may occur occasionally. Limited evidence suggests that nephrotoxicity and hyperkalemia both may occur more frequently in patients with AIDS than in other patients treated with parenteral pentamidine; hyperkalemia has been severe in some patients. Rarely, pentamidine-induced acute renal failure has been associated with myoglobinuria or gross hematuria. The risk and degree of pentamidine-induced renal impairment may be increased in the presence of dehydration or by concomitant use of other nephrotoxic drugs. Acute renal failure has been reported in at least 1 patient receiving pentamidine inhalation therapy; flank pain and nephritis also have been reported occasionally in patients receiving the aerosolized drug by oral inhalation via nebulizer.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 880
Cardiorespiratory arrest (following rapid IV injection), ventricular tachycardia, atypical ventricular tachycardia (torsade de pointes), ECG abnormalities, and facial flushing have also been reported in patients receiving parenteral pentamidine. The risk of hypotensive reactions following IM or IV administration of pentamidine isethionate has not been directly compared, but some data suggest that there is no difference in the frequency of these reactions following either route of administration when IV infusions of the drug are administered over a period of at least 60 minutes. Hypotensive reactions may be particularly likely to occur following rapid IV injection or infusion. To minimize the risk of this adverse effect when pentamidine isethionate is administered IV, infusions of the drug should be given over a period of 60-120 minutes. However, hypotension, which was not ameliorated by adjustment of the infusion rate, persisted beyond completion of the infusion, and required volume expansion for correction, has been reported in some patients. Hypotension, hypertension, tachycardia, palpitations, syncope, dizziness, light-headedness, diaphoresis, cerebrovascular accident, vasodilatation, and vasculitis have been reported occasionally in patients receiving orally inhaled pentamidine.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 880
Since pentamidine has become commercially available, there is renewed interest in using it as the initial treatment for Pneumocystis carinii pneumonia in AIDS patients. /The authors/ reviewed the use of pentamidine in 24 patients with Pneumocystis carinii pneumonia to gain information on the prevalence and severity of adverse effects from this drug. Twenty out of twenty-four patients (83 percent) experienced some kind of adverse effect. Hepatic abnormalities (58 percent), nausea and vomiting (46 percent), hypoglycemia (33 percent), azotemia (25 percent), and pain at the injection site (25 percent) were the most frequently seen effects.
PMID:3490958 Andersen R et al; Drug Intell Clin Pharm 20 (11):862-8 (1986)
For more Drug Warnings (Complete) data for PENTAMIDINE (25 total), please visit the HSDB record page.
For the treatment of pneumonia due to Pneumocystis carinii.
Pentamidine is an antiprotozoal agent. It is an aromatic diamidine, and is known to have activity against Pneumocystis carinii. The exact nature of its antiprotozoal action is unknown. in vitro studies with mammalian tissues and the protozoan Crithidia oncopelti indicate that the drug interferes with nuclear metabolism producing inhibition of the synthesis of DNA, RNA, phospholipids and proteins. Little is known about the drug's pharmacokinetics. The medication is also useful in Leishmaniasis and in prophylaxis against sleeping sickness caused by Trypanosoma brucei gambiense. Hydration before treatment lessens the incidence and severity of side effects, which include liver or kidney dysfunction, hypertension, hypotension, hypoglycemia, hypocalemia, leukopenia, thrombcytopenia, anemia, and allergic reaction. It is generally well-tolerated.
Trypanocidal Agents
Agents destructive to the protozoal organisms belonging to the suborder TRYPANOSOMATINA. (See all compounds classified as Trypanocidal Agents.)
Antifungal Agents
Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. (See all compounds classified as Antifungal Agents.)
Antiprotozoal Agents
Substances that are destructive to protozoans. (See all compounds classified as Antiprotozoal Agents.)
Absorption
Absorbed poorly through the gastrointestinal tract and is usually administered parenterally.
Pentamidine isethionate is fairly well absorbed from parenteral sites of admin despite the formation of sterile abscesses that may occur after its used. Following a single intravenous dose, the drug disappears from plasma with an apparent half-life of several min to a few hours; this is followed by a slower distribution phase and a prolonged elimination phase lasting from weeks to months. Patients with African trypanosomiasis exhibit marked interindividual variations in pharmacokinetic parameters. Their mean system plasma clearance after a single dose is about 1120 mL/min, but the volume of distribution is about 25,000 L, a finding that accounts for the prolonged average elimination half-life of about 12 days ... The renal clearance of pentamidine averages only about 2% to 11% of its systemic clearance ... but whether the drug is metabolized or excreted in bile ... is unknown. In patients receiving multiple injections of the drug over a 13-day period for treatment of pneumocystosis, drug accumulation occurs such that no steady-state plasma concn is attained ... /Pentamidine isethionate/
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1110
... After multiple parenteral doses, the liver, kidney, adrenal, and spleen of patients with AIDS contain the highest concn of drug, whereas only traces are found in the brain ... Lungs of such patients contain intermediate but therapeutic concn after 5 daily doses of 4 mg of base/kg. Higher pulmonary concn should be achieved by inhalation of pentamidine aerosols for prophylaxis or as adjunctive treatment for mild to moderate Pneumocystis carinii pneumonia; delivery of drug by this route results in little systemic absorption and decreased toxicity compared with intravenous admin in both adults and children. The actual dose delivered to the lungs depends on both the size of particles generated by the nebulizer and the patient's ventilatory patterns. /Pentamidine isethionate/
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1110
Aerosolized pentamidine produces concentrations approximately 10 to 100 times higher in the lungs than would a comparable dose of IV pentamidine.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 2337
Systemic absorption of inhaled pentamidine is minimal, with serum pentamidine concentrations less than 20 nanograms per mL after a nebulized dose of 4 mg/kg in most cases (versus 612 nanogram per mL after a single IV dose of 4 mg/kg). Peak systemic absorption occurs at, or near, completion of inhalation therapy.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 2337
For more Absorption, Distribution and Excretion (Complete) data for PENTAMIDINE (14 total), please visit the HSDB record page.
Hepatic.
By using high-performance liquid chromatography, the in vitro conversion of pentamidine to the corresponding amidoximes (N-hydroxypentamidine and N,N'-dihydroxypentamidine) was studied in supernatants of rat liver homogenate centrifuged at 9,000 x g. The presence of the two amidoxime peaks in chromatograms was confirmed by liquid secondary ion mass spectrometry and by unequivocal synthesis of the suspected metabolites. The metabolic reactions were found to be catalyzed by the cytochrome P-450 system (mixed-function oxidases). The formation of the monohydroxylated product was found to have a Km of 0.48 mM and a Vmax of 29.50 pmol/min per mg of protein, while the dihydroxylated metabolite had a Km of 0.73 mM and a Vmax of 4.10 pmol/min per mg of protein. ...
PMID:2285279 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC171904 Berger BJ et al; Antimicrob Agents Chemother 34 (9): 1678-84 (1990)
The antiprotozoal/antifungal drug pentamidine [1,5-bis(4-amidinophenoxy)pentane] has been recently shown to be metabolized by rat liver fractions to at least six putative metabolites as detected by high-performance liquid chromatography. ... In this study, the two major microsomal metabolites have been identified as the 2-pentanol and 3-pentanol analogs of pentamidine [1,5-di(4-amidinophenoxy)-2-pentanol; and 1,5-bis(4-amidinophenoxy)-3-pentanol]. As well, a seventh putative metabolite has been discovered and identified as para-hydroxybenzamidine, a fragment of the original drug. ... the cytochromes P-450 have been demonstrated as the enzyme system responsible for pentamidine metabolism ... the mixed-function oxidases readily convert pentamidine to hydroxylated metabolites, but exactly which isozyme(s) of cytochrome P-450 is responsible is not clear.
PMID:2005586 Berger BJ et al; J Pharmacol Exp Ther 256 (3): 883-9 (1991)
The antiprotozoal drug pentamidine [1,5-bis(4'-amidinophenoxy)pentane] has been previously shown to be metabolized by rat liver microsomes, and five of the seven putative primary metabolites have been identified. With the synthesis and identification of 5-(4'-amidinophenoxy)pentanoic acid and 5-(4'-amidinophenoxy)-1-pentanol as the remaining two metabolites, the primary metabolism of pentamidine in rats appears fully characterized. ... Isolated, perfused rat livers were used with [14C]pentamidine to identify secondary metabolites. Only two novel radioactive peaks were detected by HPLC analysis of perfused liver samples. The treatment of liver samples with sulfatase or beta-glucuronidase resulted in the reduction or elimination of these peaks and gave rise to peaks identified as para-hydroxybenzamidine and 5-(4'-amidinophenoxy)pentanoic acid. It was concluded from these results that only these two primary metabolites were conjugated with sulfate or glucuronic acid.
PMID:1416874 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC192194 Berger BJ et al; Antimicrob Agents Chemother 36 (9): 1825-31 (1992)
Pentamidine /is a substrate for/ human liver microsomal P450 enzyme CYP2C19. /From table/
Klaassen, C.D. (ed). Casarett and Doull's Toxicology. The Basic Science of Poisons. 6th ed. New York, NY: McGraw-Hill, 2001., p. 184
9.1-13.2 hours
Intramuscular: 9.1 to 13.2 hours. Intravenous: Approximately 6.5 hours. Terminal half-life: 2 to 4 weeks. Renal function impairment: Pentamidine half-life may be prolonged in patients with renal dysfunction ; however, no correlation between renal function and plasma clearance of pentamidine has been found.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007.
The mode of action of pentamidine is not fully understood. It is thought that the drug interferes with nuclear metabolism producing inhibition of the synthesis of DNA, RNA, phospholipids, and proteins.
... Up to now, it has been thought that therapeutic compounds causing QT prolongation are associated with direct block of the cardiac potassium channel human ether a-go-go-related gene (hERG), which encodes the alpha subunit of cardiac I(Kr) currents. /The authors/ show that pentamidine has no acute effects on currents produced by hERG, KvLQT1/mink, Kv4.3, or SCNA5. Cardiac calcium currents and the guinea pig cardiac action potential were also not affected. After overnight exposure, however, pentamidine reduced hERG currents and inhibited trafficking and maturation of hERG with IC(50) values of 5 to 8 uM similar to therapeutic concentrations. Surface expression determined in a chemiluminescence assay was reduced on exposure to 10, 30, and 100 uM pentamidine by about 30, 40, and 70%, respectively. These effects were specific for hERG since expression of hKv1.5, KvLQT1/minK, and Kv4.3 was not altered. In isolated guinea pig ventricular myocytes, 10 uM pentamidine prolonged action potential duration APD(90) from 374.3 or + or - 57.1 to 893.9 + or - 86.2 ms on overnight incubation. I(Kr) tail current density was reduced from 0.61 + or - 0.09 to 0.39 + or - 0.04 pA/pF. /The authors/ conclude that pentamidine prolongs the cardiac action potential by block of hERG trafficking and reduction of the number of functional hERG channels at the cell surface. /The authors/ propose that pentamidine, like arsenic trioxide, produces QT prolongation and torsades de pointes in patients by inhibition of hERG trafficking.
PMID:15340016 Kuryshev YA et al; J Pharmacol Exp Ther 312 (1): 316-23 (2005)
... Inhibition in vitro of trypanosomal mitochondrial topoisomerase II and plasma Ca+2, Mg+2-ATPase also has been reported ... Pentamidine promotes linearization of trypanosome kinetoplast DNA, consistent with its being a type II topoisomerase inhibitor ... The drug also inhibits ATP-dependent topoisomerases in extracts of Pneumocystis carinii ...
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1110
Not clearly defined; pentamidine may interfere with incorporation of nucleotides into RNA and DNA and inhibit oxidative phosphorylation and biosynthesis of DNA, RNA, protein, and phospholipid; may also interfere with folate transformation.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007.
... The cytotoxic properties of pentamidine isethionate (2) towards the promastigotes of the protozoan parasite Leishmania infantum /was determined/. The leishmanicidal activity of 2 was 60 times higher after 72 hr of incubation than that of cisplatin. The pentamidine salt 2 induced a higher amount of programmed cell death (PCD) than cisplatin, which is associated with inhibition of DNA synthesis and cell-cycle arrest in the G2/M phase. Circular dichroism (CD) data indicate that binding of 2 to calf-thymus DNA (CT-DNA) induces conformational changes in the DNA double helix, consistent with a B-->A transition. Moreover, the interaction of 2 with ubiquitin led to a 6% increase in the beta-sheet content of the protein as observed by CD spectroscopy. Fluorescence-spectroscopy studies agreed with the CD data, showing that the pentamidine portion of 2 induces a significant decrease in the fluorescence of the Ub residues Phe4 and Phe45 located on the beta-cluster of the molecule, but not of Tyr59 on the alpha-cluster. These data indicate that pentamidine specifically modifies the beta-cluster, i.e., the 'basic face' of ubiquitin. ... /The/ results suggest that the biochemical mechanism of action of pentamidine may be a consequence of its dual binding to DNA and proteins.
PMID:7191940 Nguewa PA et al; Chem Biodivers 2 (10): 1387-400 (2005)
In this work pentamidine is shown to exhibit characteristics of a cationic uncoupler of oxidative phosphorylation in isolated rat liver mitochondria: it released respiratory control, enhanced the latent ATPase activity, and released the inhibition of State 3 respiration by oligomycin. Maximal stimulation of respiration and ATPase activity was observed at a concentration of pentamidine of 200-300 microM. Higher concentrations had an inhibitory effect on mitochondrial respiration. As it happens with other cationic uncouplers, the uncoupling effect of pentamidine required inorganic phosphate. Pentamidine-induced uncoupling of oxidative phosphorylation was accompanied by an efflux of Ca2+ from the mitochondria and partial collapse of the mitochondrial membrane potential.
PMID:8579363 Moreno SN; Arch Biochem Biophys 326 (1): 15-20 (1996)
Digital Content 
NEWS #PharmaBuzz
Global Sales Information
Market Place
ABOUT THIS PAGE
LOOKING FOR A SUPPLIER?
