Disease relevance of pentamidine

• Severe hemorrhagic pancreatitis developed in a patient with the acquired immunodeficiency syndrome (AIDS) during pentamidine isethionate treatment for Pneumocystis carinii pneumonia [1].
• To determine whether opportunistic infection in children without underlying immunodeficiency was truly a new phenomenon, a review of requests to the CDC for the drug pentamidine isethionate was undertaken [2].
• In 1984, three patients died of severe hypoglycemia after receiving pentamidine isethionate to treat Pneumocystis pneumonia [3].
• We compared the efficacy of amphotericin B and pentamidine isethionate in a prospective randomised trial in 120 uncomplicated and parasitologically confirmed cases of antimony-unresponsive kala-azar [4].
• Interventions: Pentamidine isethionate, 4 mg/kg body weight by inhalation, or 3 mg/kg intravenously, was given once daily, as long as clinically indicated [5].

High impact information on pentamidine

• INTERVENTIONS: Pentamidine isethionate, 600 mg by inhalation using a Respirgard II nebulizer (Marquest Medical Products, Inc., Englewood, Colorado) or 3 mg/kg body weight intravenously, administered once daily for 2 to 3 weeks [6].
• Pentamidine isethionate reduces Ia expression and antigen presentation by Langerhans cells and inhibits the contact hypersensitivity reaction [7].
• Ventricular tachycardia due to pentamidine isethionate [8].
• Two drugs, pentamidine isethionate and trimethoprimsulfamethoxazole, are equally effective therapeutically - permitting the recovery of approximately 75% of patients - but the latter drug combination is preferred because of its lower toxicity and fewer adverse effects [9].
• Torsade de pointes during administration of pentamidine isethionate [10].

Chemical compound and disease context of pentamidine

• Forty patients with the acquired immunodeficiency syndrome (AIDS) and their first episodes of Pneumocystis carinii pneumonia were assigned at random to receive either trimethoprim-sulfamethoxazole or pentamidine isethionate [11].
• Two patients receiving pentamidine isethionate for the treatment of Pneumocystis carinii experienced acute pancreatitis temporally related to pentamidine therapy [12].
• This has been clearly demonstrated in the case of the melamine-based arsenical and the diamidine classes of drug that are already in use in the treatment of human African trypanosomiasis [13].
• New platinum- and rhodium-metal complexes of diamidine and plenanthridinium trypanocides are described which showed higher therapeutic indices than the parent drugs, due to increased activity in the former drug type and decreased toxicity in the latter [14].
• The trypanocidals diminazene (equivalent to Berenil) and pentamidine (equivalent to Lomidine), together with aprotinin (Trasylol), showed most promise when considering possible applications in mastitis to break up the proteolytic cascade within the inflamed udder [15].

Biological context of pentamidine

• Cooperative dimerization of a heterocyclic diamidine determines sequence-specific DNA recognition [16].
• The data provide clues for delineating a recognition code for diamidine-type minor groove binding agents, and ultimately to guide the rational design of gene regulatory molecules targeted to specific sites of the genetic material [17].
• We used a new high-performance liquid-chromatography assay to study the pharmacokinetics of pentamidine isethionate given intravenously to 10 dogs before and after surgically induced renal failure [18].
• These data together indicate that diamidine drugs accumulate in the Leishmania mitochondrion and that the development of the resistance phenotype is accompanied by lack of mitochondrial accumulation of the drug and its exclusion from the parasites [19].
• Collectively, the SPR and footprinting results show that the consensus sequence 5'-(A/T)-TG-(A/T) represents the optimal site for cooperative dimerization of the heterocyclic diamidine DB293 [16].

Anatomical context of pentamidine

• The new aza analog, DB820, is the active diamidine of the prodrug DB844, currently undergoing preclinical evaluation as a new candidate to treat HAT of the central nervous system [20].
• Therapeutic concentrations (0.3-1.5 mg/l) of pentamidine isethionate and pentamidine mesylate, obtained after parenteral administration of either drug, did not affect oxygen consumption in the stimulated neutrophilic granulocyte [21].
• The antiprotozoan and antifungal agent, the terbinafine, was investigated for its potential activity against Pneumocystis carinii infection of the A549 cell line culture and on immunosuppressed Sprague Dawley rats in comparison with trimethoprim-sulphamethoxazole and pentamidine isethionate [22].
• We conclude that pancreatitis is common in pediatric patients with AIDS and may be related to pentamidine isethionate exposure, especially when absolute CD4 T-lymphocyte counts are less than 100 cells/mm3 [23].
• To further elucidate, FG and another aromatic diamidine, pentamidine, were tested on [3H]DA release and uptake in vitro from striatal slices and synaptosomes [24].

Associations of pentamidine with other chemical compounds

• Surveillance has been predominantly passive, supplemented by active follow-up of requests to the Centers for Disease Control for pentamidine isethionate for treatment of Pneumocystis carinii pneumonia [25].
• Trimethoprim-sulfamethoxazole and pentamidine isethionate have been used extensively for the prophylaxis and therapy of pneumonia caused by Pneumocystis jirovecii [26].
• The energetics for binding of a diphenyl diamidine antitrypanosomal agent CGP 40215A to DNA have been studied by spectroscopy, isothermal titration calorimetry, and surface plasmon resonance biosensor methods [27].
• An unusual amino-purine transporter termed P2, implicated in the transport of both the diamidine and melaminophenyl arsenical classes of drug in Trypanosoma brucei, recognised chemical groups on compounds which are also present on megazol [28].
• These findings further characterize distinguishing features of the unique AdoMet transporter in African trypanosomes, and indicate that the P2 adenosine transporter remains functional in melarsen- and diamidine-resistant clinical isolates [29].

Gene context of pentamidine

• The intralesional expression of cytokines (interleukin [IL]-4, IL-13, IL-10, and interferon-gamma) was analyzed in 65 patients with localized cutaneous leishmaniasis due to Leishmania guyanensis before specific treatment with pentamidine isethionate [30].
• The study of the induction of apoptosis was carried out by 4'-6-diamidine-2'-phenylindole (DAPI) staining of segmented nuclei, western blot of p53 protein and TdT-mediated dUTP-biotin nick end labeling (TUNEL) method, while the interaction with DNA was evaluated through the analysis of interstrand cross-link (ISCL) formation [31].
• Preincubation of CD4 lymphocytes with pentamidine isethionate at a concentration of 1.5 mg/L then removal from incubation medium prior to addition of HIV-1, or incubation of cells with the drug and virus simultaneously, increased HIV-1 DNA load but reduced p24 antigen release [32].
• Each of the three diamidines investigated (pentamidine isothionate, amicarbilide and M and B 4596) exhibited marked antileishmanial activity, but only M and B 4596 had any significant effect (36% inhibition at 33 microgram/ml) on L. m. mexicana amastigote proteinase activity [33].
• The aromatic diamidine berenil specifically inhibits the condensation of a subset of constitutive heterochromatin in human lymphocyte cultures [34].

Analytical, diagnostic and therapeutic context of pentamidine

• Over-all, the rate of recovery from Pneumocystis pneumonia after treatment with pentamidine isethionate was 41 percent [35].
• In an effort to develop biologically active minor groove agents, we are preparing and exploring the DNA interactions of a systematic set of diamidine derivatives with a powerful array of methods including DNase I footprinting, biosensor-SPR methods, and X-ray crystallography [36].
• The diphenyl furan diamidine, DB75, is the active metabolite of the prodrug DB289, which is currently in phase III clinical trials as a new orally active candidate drug to treat first-stage HAT [20].
• Although the growth characteristics of Pneumocystis carinii have been described in several cell culture systems, the response of this organism to the drugs of choice, trimethoprim-sulfamethoxazole and pentamidine isethionate, have not been described in vitro [37].
• Failure of pentamidine isethionate to provide chemoprophylaxis against Pneumocytis carinii infection in rats [38].

References