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Reviews of Infectious Diseases 1985Pentamidine, recently released for clinical use, is effective in therapy for the hemolymphatic stage of Gambian trypanosomiasis, antimony-resistant leishmaniasis, and... (Clinical Trial)
Clinical Trial Review
Pentamidine, recently released for clinical use, is effective in therapy for the hemolymphatic stage of Gambian trypanosomiasis, antimony-resistant leishmaniasis, and Pneumocystis carinii pneumonia. The mechanism of action is unclear and may differ for different organisms. Trypanosomes actively transport pentamidine intracellularly, and the drug may then interfere with DNA biosynthetics. However, pentamidine appears to kill nonreplicating P. carinii. The mechanism of killing is unexplained. The pharmacokinetics of pentamidine has been incompletely studied in humans. The estimated volume of distribution is 3 liters/kg. Levels in plasma of pentamidine range from 0.3-1.4 microgram/ml after standard 4 mg/kg dosing, with no appreciable increase in drug levels on successive dosing and no correlation between levels and creatinine clearance or adverse reactions. The drug appears to be concentrated in the kidney and excreted in the urine, with levels detectable six to eight weeks after cessation of therapy. Immediate adverse reactions have included hypotension, nausea, and vomiting. Local pain or abscess formation at an injection site, mild azotemia, leukopenia, abnormal findings from liver function tests, and hypoglycemia may also occur.
Topics: Amidines; Animals; Babesiosis; Clinical Trials as Topic; Disease Models, Animal; Drug Resistance, Microbial; Humans; In Vitro Techniques; Kidney; Kinetics; Leishmaniasis; Pentamidine; Pneumonia, Pneumocystis; Trypanosoma brucei gambiense; Trypanosomiasis, African
PubMed: 3903942
DOI: 10.1093/clinids/7.5.625 -
Infection Control and Hospital... Jun 1991
Comparative Study Review
Topics: Acquired Immunodeficiency Syndrome; Administration, Inhalation; Animals; Half-Life; Humans; Metabolic Clearance Rate; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 2071882
DOI: 10.1086/646360 -
Drug Safety 1990With the advent of the acquired immunodeficiency syndrome (AIDS), the therapeutic importance of pentamidine isethionate has greatly increased. This review summarises its... (Review)
Review
With the advent of the acquired immunodeficiency syndrome (AIDS), the therapeutic importance of pentamidine isethionate has greatly increased. This review summarises its pharmacology, its toxicity and clinical experience in the treatment of Pneumocystis carinii pneumonia (PCP). Data are conflicting as to whether pentamidine is more or less effective than cotrimoxazole (trimethoprim-sulfamethoxazole) for the treatment of PCP in individuals with AIDS, but due to its toxicity and expense, it is considered as second-line therapy by many authorities. Hypoglycaemia has been encountered in up to 27% of treatment courses with pentamidine, and nephrotoxicity in 25%. In an attempt to circumvent the toxicities associated with parenteral administration, aerosolised delivery has been evaluated for both therapy and prevention of PCP. Aerosolised pentamidine, on the basis of early clinical results, convenience and low toxicity, may become the drug of choice for prevention of PCP in individuals at high risk. However, its role in the treatment of PCP remains to be defined. Preliminary studies suggest that it is effective, but the data are insufficient to support its use outside of clinical trials.
Topics: Humans; Pentamidine; Risk Factors
PubMed: 2190597
DOI: 10.2165/00002018-199005030-00006 -
Current Medicinal Chemistry 2022Pentamidine, an FDA-approved human drug for many protozoal infections, was initially synthesized in the late 1930s and first reported to be curative for parasitosis in... (Review)
Review
Pentamidine, an FDA-approved human drug for many protozoal infections, was initially synthesized in the late 1930s and first reported to be curative for parasitosis in the 1940s. After ninety years of sometimes quiet growth, pentamidine and its derivatives have gone far beyond antibacterial agents, including but not limited to the ligands of DNA minor groove, modulators of PPIs (protein-protein interactions) of the transmembrane domain 5 of lateral membrane protein 1, and the blockers of the SARS-CoV-2 3a channel. This mini-review highlights the development and applications of pentamidine and its analogs, aiming to provide insights for further developing pentamidine derivatives in the following decades.
Topics: DNA; Humans; Ligands; Pentamidine; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35289252
DOI: 10.2174/0929867329666220314121446 -
Frontiers in Immunology 2023Immunotherapy has emerged as an effective therapeutic approach to several cancer types. The reinvigoration of tumor-infiltrating lymphocyte-mediated immune responses...
Immunotherapy has emerged as an effective therapeutic approach to several cancer types. The reinvigoration of tumor-infiltrating lymphocyte-mediated immune responses the blockade of immune checkpoint markers, such as program cell death-1 (PD-1) or its cognate ligand PD-L1, has been the basis for developing clinically effective anticancer therapies. We identified pentamidine, an FDA-approved antimicrobial agent, as a small-molecule antagonist of PD-L1. Pentamidine enhanced T-cell-mediated cytotoxicity against various cancer cells by increasing the secretion of IFN-γ, TNF-α, perforin, and granzyme B in the culture medium. Pentamidine promoted T-cell activation by blocking the PD-1/PD-L1 interaction. administration of pentamidine attenuated the tumor growth and prolonged the survival of tumor-bearing mice in PD-L1 humanized murine tumor cell allograft models. Histological analysis of tumor tissues showed an increased number of tumor-infiltrating lymphocytes in tissues derived from pentamidine-treated mice. In summary, our study suggests that pentamidine holds the potential to be repurposed as a novel PD-L1 antagonist that may overcome the limitations of monoclonal antibody therapy and can emerge as a small molecule cancer immunotherapy.
Topics: Mice; Animals; Pentamidine; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Immunotherapy; Neoplasms
PubMed: 37205112
DOI: 10.3389/fimmu.2023.1145028 -
Current Medicinal Chemistry 2012Sixty years after its introduction, 1,5-bis(4-amidinophenoxy)pentane (Pentamidine) is still one of the most used drugs for the treatment of the first stage of Human... (Review)
Review
Sixty years after its introduction, 1,5-bis(4-amidinophenoxy)pentane (Pentamidine) is still one of the most used drugs for the treatment of the first stage of Human African trypanosomiasis and other neglected diseases such as malaria and leishmaniasis. These protozoan infections are prevalent in the poorest world areas such as sub-saharian and developing countries, however the increasing immigration from these countries to the richest part of the world and the overlap of HIV with parasitic infections result in a growing number of cases in developed nations. A great effort has been made to develop new generations of diamidines for the treatment of these infections transmitted by insects. This review summarises the synthesis and evaluation of pentamidine analogues reported in the last years in the effort to find new drugs with better pharmaceutical activity, higher lipophilicity and lower citotoxycicty.
Topics: Antiprotozoal Agents; Chemistry, Pharmaceutical; Drug Design; Humans; Pentamidine; Trypanosoma; Trypanosomiasis, African
PubMed: 23092128
DOI: 10.2174/092986712804143268 -
Clinical Pharmacy 1985The chemistry, antiprotozoal activity, pharmacology, clinical efficacy, adverse effects, dosage, administration, and hospital formulary considerations of pentamidine... (Review)
Review
The chemistry, antiprotozoal activity, pharmacology, clinical efficacy, adverse effects, dosage, administration, and hospital formulary considerations of pentamidine isethionate are reviewed. Pentamidine, an aromatic diamidine, has been used since the 1940s to treat a variety of protozoal infections. It is now most commonly administered in the treatment of Pneumocystis carinii pneumonia (PCP). It is generally not metabolized, and it is stored or bound to tissue and excreted slowly as the parent compound. Pentamidine is clearly effective in the treatment of PCP; however, the high incidence of adverse reactions associated with the drug led to the use of trimethoprim-sulfamethoxazole (TMP-SMX) as the first-line agent for PCP. Recent studies have reported a high incidence of adverse reactions, including leukopenia and hepatotoxicity, associated with the use of TMP-SMX therapy for PCP in patients with the acquired immunodeficiency syndrome (AIDS). The severity and frequency of these reactions suggest a possible new role for pentamidine in patients with AIDS who have PCP. The recommended intramuscular and intravenous dosage of pentamidine isethionate for adults and children is 4 mg/kg/day for 14 days. Intramuscular administration is recommended; however, intravenous administration is a safe alternative if the dose is infused over a 60-minute period. Pentamidine isethionate has specific application in the treatment of PCP as a second-line agent reserved for patients who cannot tolerate TMP-SMX.
Topics: Amidines; Antiprotozoal Agents; Chemical Phenomena; Chemistry; Costs and Cost Analysis; Drug Compounding; Formularies as Topic; Humans; Kinetics; Pentamidine; Pneumonia, Pneumocystis
PubMed: 3902329
DOI: No ID Found -
Journal of Pediatric Oncology Nursing :... Apr 1994
Topics: Adolescent; Child; Drug Stability; Humans; Neoplasms; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis
PubMed: 8003265
DOI: 10.1177/104345429401100208 -
Lancet (London, England) Mar 1989
Topics: Aerosols; Amidines; Evaluation Studies as Topic; Humans; Nebulizers and Vaporizers; Pentamidine
PubMed: 2563874
DOI: 10.1016/s0140-6736(89)91404-9 -
Transactions of the Royal Society of... 1984Twelve cases of diabetes mellitus following pentamidine isethionate ( Lomidine ) treatment for antimonial -resistant cases of kala-azar are reported. 11 were found to be...
Twelve cases of diabetes mellitus following pentamidine isethionate ( Lomidine ) treatment for antimonial -resistant cases of kala-azar are reported. 11 were found to be insulin-dependent and one insulin-independent. One patient died at home two months later and the rest still had diabetes mellitus at follow-up after two to five years.
Topics: Amidines; Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; Leishmaniasis, Visceral; Pentamidine
PubMed: 6464116
DOI: 10.1016/0035-9203(84)90289-x