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Mayo Clinic Proceedings Jan 2021
Topics: Central Venous Catheters; Hematopoietic Stem Cell Transplantation; Humans; Infusions, Intravenous; Male; Middle Aged; Pentamidine; Thrombophlebitis
PubMed: 33413823
DOI: 10.1016/j.mayocp.2020.10.023 -
Medizinische Klinik (Munich, Germany :... Apr 1990The incidence of systemic side effects under aerosolized pentamidine treatment or prophylaxis for pneumocystis carinii pneumonia is low when compared to intravenous... (Review)
Review
The incidence of systemic side effects under aerosolized pentamidine treatment or prophylaxis for pneumocystis carinii pneumonia is low when compared to intravenous application. Erythema, hypotension, hypoglycemia, renal failure are infrequently seen. Local side effects--cough, bronchial spasm, metallic taste--are frequent complications of aerosolized pentamidine treatment. Cystic lung disease, pneumothorax, and atypical pneumonia may be a late sequelae of pneumocystis carinii pneumonia, and not a primary effect of pentamidine. Poor apical ventilation due to suboptimal inhalation technique etc. and decreased deposition of pentamidine in these areas may be of some consequence for the development of these unusual complications. Extrapulmonary pneumocystis infections under preventive pentamidine aerosol treatment for pneumocystis carinii pneumonia have been seen in single cases, a causal relationship to pentamidine application is not yet established.
Topics: Acquired Immunodeficiency Syndrome; Administration, Inhalation; Humans; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis
PubMed: 2197533
DOI: No ID Found -
Nanotechnology Nov 2019Leishmaniasis is a group of diseases caused by a protozoa parasite from one of over 20 Leishmania species. Depending on the tissues infected, these diseases are...
Leishmaniasis is a group of diseases caused by a protozoa parasite from one of over 20 Leishmania species. Depending on the tissues infected, these diseases are classified as cutaneous, mucocutaneous and visceral leishmaniasis. For the treatment of leishmaniasis refractory to antimony-based drugs, pentamidine (PTM) is a molecule of great interest. However, PTM displays poor bioavailability through oral routes due to its two strongly basic amidine moieties, which restricts its administration by a parenteral route and limits its clinical use. Among various approaches, nanotechnology-based drug delivery systems (nano-DDS) have potential to overcome the challenges associated with PTM oral administration. Here, we present the development of PTM-loaded PLGA nanoparticles (NPs) with a focus on the characterization of their physicochemical properties and potential application as an oral treatment of leishmaniasis. NPs were prepared by a double emulsion methodology. The physicochemical properties were characterized through the mean particle size, polydispersity index (PdI), zeta potential, entrapment efficiency, yield process, drug loading, morphology, in vitro drug release and in vivo pharmacological activity. The PTM-loaded PLGA NPs presented with a size of 263 ± 5 nm (PdI = 0.17 ± 0.02), an almost neutral charge (-3.2 ± 0.8 mV) and an efficiency for PTM entrapment of 91.5%. The release profile, based on PTM dissolution, could be best described by a zero-order model, followed by a drug diffusion profile that fit to the Higuchi model. In addition, in vivo assay showed the efficacy of orally given PTM-loaded PLGA NPs (0.4 mg kg) in infected BALB/c mice, with significant reduction of organ weight and parasite load in spleen (p-value < 0.05). This work successfully reported the oral use of PTM-loaded NPs, with a high potential for the treatment of visceral leishmaniasis, opening a new perspective to utilization of this drug in clinical practice.
Topics: Administration, Oral; Animals; Antiprotozoal Agents; Biological Availability; Disease Models, Animal; Leishmaniasis; Mice; Mice, Inbred BALB C; Nanoparticles; Organ Size; Parasite Load; Particle Size; Pentamidine; Polylactic Acid-Polyglycolic Acid Copolymer
PubMed: 31365912
DOI: 10.1088/1361-6528/ab373e -
Dermatologica 1991Pentamidine is one of two agents currently used to treat infections with Pneumocystis carinii. The intramuscular route of administration is associated with cutaneous... (Review)
Review
Pentamidine is one of two agents currently used to treat infections with Pneumocystis carinii. The intramuscular route of administration is associated with cutaneous side effects such as dermal necrosis, sterile abscesses and ulcer formation at the injection site, while urticaria may develop near the site of intravenous drug infusion. This is a report of a renal transplant patient with Pneumocystis pneumonia who developed chemical cellulitis and ulceration following the extravasation of intravenous pentamidine into the soft tissues of the left hand and forearm. The area healed slowly over 7 weeks, but there was a residual loss of cutaneous sensation. In a review of the literature no report of a similar case was found.
Topics: Adult; Female; Forearm; Hand Dermatoses; Humans; Injections, Intravenous; Kidney Transplantation; Pentamidine; Pneumonia, Pneumocystis; Skin Ulcer
PubMed: 1743388
DOI: 10.1159/000247675 -
Pharmacy World & Science : PWS Aug 1996In our hospital safety guidelines are available for the handling of pentamidine in the day-care department, but no safety ventilation cabin is used because only one...
In our hospital safety guidelines are available for the handling of pentamidine in the day-care department, but no safety ventilation cabin is used because only one patient a day has been treated, The number of patients to be treated, however, is growing, resulting in the need to treat more than one patient a day. To determine the environmental contamination and exposure of health-care workers during and after aerosolised pentamidine treatment of more than one patient with the acquired immunodeficiency syndrome a day a high-performance liquid chromatographic method is used for the detection and quantification of pentamidine. High volume air samples were taken before, immediately after and the day after a treatment session of up to three patients. Also, sediment samples and personal air samples close to the mouth of the health-care workers were taken. Immediately after a treatment session the air in the room contains 1.0-99.7 micrograms pentamidine per m3 of air. Before and the morning after treatment no pentamidine could be detected in the air. Sediment samples vary in detectable amounts of pentamidine from < 5 to 1165 micrograms. pentamidine/cm2. The personal air samples also show a large variation in quantities of pentamidine: < 5-170 ng a filter. When large amounts of pentamidine in the high volume air samples are found high amounts of pentamidine on the sediment samples and the personal air samples are found as well. This means that the patients treated should be instructed well on how to use the nebulizer correctly and be monitored during treatment. Additional safety measures (for example the use of a safety ventilation cabin) should be taken when more than one patient is treated a day.
Topics: Aerosols; Air Pollutants, Occupational; Allied Health Personnel; Analysis of Variance; Antiprotozoal Agents; Chromatography, High Pressure Liquid; Humans; Occupational Exposure; Pentamidine
PubMed: 8873231
DOI: 10.1007/BF00717731 -
Frontiers in Cellular and Infection... 2022Fungal infection is a serious global health issue, causing approximately 1.5 million mortalities annually. However, clinically available anti-fungal drugs are limited,...
Fungal infection is a serious global health issue, causing approximately 1.5 million mortalities annually. However, clinically available anti-fungal drugs are limited, especially for multidrug-resistant fungal infections. Therefore, new antifungal drugs are urgently needed to address this clinical challenge. In this study, we proposed two non-antifungal drugs, auranofin and pentamidine, in combination to fight against multidrug-resistant . The insufficient antifungal activity of anti-rheumatic drug auranofin is partially due to fungal membrane barrier preventing the drug uptake, and anti-protozoal drug pentamidine was used here to improve the permeability of membrane. The auranofin/pentamidine combination displayed synergistic inhibitory effect against both drug-susceptible and drug-resistant , as well as biofilm, and significantly reduced the minimum inhibitory concentration of each drug. At non-antifungal concentration, pentamidine can disrupt the membrane integrity and increase membrane permeability, leading to enhanced cellular uptake of auranofin in . This repurposing strategy using the combination of non-antifungal drugs with complementary antifungal mechanism may provide a novel approach for discovery of antifungal drugs to fight against multidrug-resistant fungal infections.
Topics: Antifungal Agents; Candida albicans; Pentamidine; Auranofin; Drug Repositioning; Microbial Sensitivity Tests
PubMed: 36590591
DOI: 10.3389/fcimb.2022.1065962 -
The Western Journal of Medicine Jul 1990
Review
Topics: Aerosols; HIV Seropositivity; Humans; Liver; Male; Middle Aged; Necrosis; Pentamidine; Pneumonia, Pneumocystis; Spleen
PubMed: 2202161
DOI: No ID Found -
Pharmacology & Toxicology Jan 1994The subcellular distribution and the effects of pentamidine on the ultrastructure of the rat liver were studied. Rats were given single or repeated daily intraperitoneal...
The subcellular distribution and the effects of pentamidine on the ultrastructure of the rat liver were studied. Rats were given single or repeated daily intraperitoneal injections of 10, 25 or 50 mg pentamidine isethionate/kg b. wt. for 1, 4, 6, 9 or 16 days. The livers were removed for ultrastructural and biochemical analyses on the day after termination of each series of injections and in addition 7 and 35 days after the 16th injection. Electron microscopy of liver tissues showed that the general cellular architecture of the hepatocytes was preserved. The subcellular organelles were normal, except for the secondary lysosomes, which were severely altered and laden with multilamellar, myelin structures (myelin bodies) that gradually increased with dose and time course following repeated injections. These altered lysosomes were enriched in phospholipids. The alteration of the lysosomes persisted for up to 5 weeks after cessation of administration. Pentamidine was highly enriched in the lysosomal fraction (30-50 times more than in the liver homogenate). It was calculated that the lysosomal pentamidine accounted for practically all pentamidine distributed to the liver. The demonstrated accumulation of pentamidine in the lysosomes may explain the known large volume of distribution of this drug and may be one mechanism for organ toxicity.
Topics: Animals; Liver; Lysosomes; Male; Pentamidine; Phospholipids; Rats; Rats, Sprague-Dawley; Subcellular Fractions
PubMed: 8159632
DOI: 10.1111/j.1600-0773.1994.tb01067.x -
The New England Journal of Medicine Sep 1985
Topics: Amidines; Diarrhea; Humans; Injections, Intramuscular; Injections, Intravenous; Kidney Diseases; Pentamidine
PubMed: 4022063
DOI: No ID Found -
PLoS Neglected Tropical Diseases May 2008Pentamidine has a long history in the treatment of human African trypanosomiasis (HAT) and leishmaniasis. Early guidelines on the dosage of pentamidine were based on the...
Pentamidine has a long history in the treatment of human African trypanosomiasis (HAT) and leishmaniasis. Early guidelines on the dosage of pentamidine were based on the base-moiety of the two different formulations available. Confusion on the dosage of pentamidine arose from a different labelling of the two available products, either based on the salt or base moiety available in the preparation. We provide an overview of the various guidelines concerning HAT and leishmaniasis over the past decades and show the confusion in the calculation of the dosage of pentamidine in these guidelines and the subsequent published reports on clinical trials and reviews. At present, only pentamidine isethionate is available, but the advised dosage for HAT and leishmaniasis is (historically) based on the amount of pentamidine base. In the treatment of leishmaniasis this is probably resulting in a subtherapeutic treatment. There is thus a need for a new, more transparent and concise guideline concerning the dosage of pentamidine, at least in the treatment of HAT and leishmaniasis.
Topics: Antiprotozoal Agents; Guidelines as Topic; Humans; Leishmaniasis; Pentamidine; Trypanocidal Agents; Trypanosomiasis, African
PubMed: 18509543
DOI: 10.1371/journal.pntd.0000225