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The American Journal of Medicine Apr 1995
Topics: AIDS-Related Opportunistic Infections; Aerosols; Clinical Trials as Topic; Humans; Pentamidine; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 7709963
DOI: 10.1016/s0002-9343(99)80335-0 -
American Heart Journal May 1992
Review
Topics: Adult; Female; Humans; Infusions, Intravenous; Male; Pentamidine; Pneumonia, Pneumocystis; Time Factors; Torsades de Pointes
PubMed: 1575157
DOI: 10.1016/0002-8703(92)91047-5 -
The American Journal of Tropical... Nov 2018Bolivian cutaneous leishmaniasis due to was treated with the combination of miltefosine (150 mg/day for 28 days) plus intralesional pentamidine (120 μg/mm lesion area...
Bolivian cutaneous leishmaniasis due to was treated with the combination of miltefosine (150 mg/day for 28 days) plus intralesional pentamidine (120 μg/mm lesion area on days 1, 3, and 5). Ninety-two per cent of 50 patients cured. Comparison to historic controls at our site suggests that the efficacy of the two drugs was additive. Adverse effects and cost were also additive. This combination may be attractive when a prime consideration is efficacy (e.g., in rescue therapy), avoidance of parenteral therapy, or the desire to treat locally and also provide systemic protection against parasite dissemination.
Topics: Adult; Antiprotozoal Agents; Bolivia; Drug Therapy, Combination; Female; Humans; Leishmania; Leishmania braziliensis; Leishmaniasis, Cutaneous; Male; Pentamidine; Phosphorylcholine; Treatment Outcome
PubMed: 30255833
DOI: 10.4269/ajtmh.18-0183 -
ChemMedChem Dec 2011Pentamidine is an effective antimicrobial agent that is approved for the treatment of African trypanosomiasis but suffers from poor oral bioavailability and central...
Pentamidine is an effective antimicrobial agent that is approved for the treatment of African trypanosomiasis but suffers from poor oral bioavailability and central nervous system (CNS) penetration. This work deals with the development and systematic characterisation of new prodrugs of pentamidine. For this reason, numerous prodrugs that use different prodrug principles were synthesised and examined in vitro and in vivo. Another objective of the study was the determination of permeability of the different pentamidine prodrugs. While some of the prodrug principles applied in this study are known, such as the conversion of the amidine functions into amidoximes or the O-alkylation of amidoximes with a carboxymethyl residue, others were developed more recently and are described here for the first time. These newly developed methods aim to increase the affinity of the prodrug for the transporters and mediate an active uptake via carrier systems by conjugation of amidoximes with compounds that improve the overall solubility of the prodrug. The different principles chosen resulted in several pentamidine prodrugs with various advantages. The objective of this investigation was the systematic characterisation and evaluation of eight pentamidine prodrugs in order to identify the most appropriate strategy to improve the properties of the parent drug. For this reason, all prodrugs were examined with respect to their solubility, stability, enzymatic activation, distribution, CNS delivery, and oral bioavailability. The results of this work have allowed reliable conclusions to be drawn regarding the best prodrug principle for the antiprotozoal drug pentamidine.
Topics: Administration, Oral; Animals; Antiprotozoal Agents; Cell Line; Cell Membrane Permeability; Cytochrome P-450 Enzyme System; Drug Stability; Humans; Hydrogen-Ion Concentration; Male; Microsomes, Liver; Pentamidine; Prodrugs; Protein Binding; Rats; Rats, Sprague-Dawley; Swine; Tissue Distribution
PubMed: 21984033
DOI: 10.1002/cmdc.201100422 -
The Journal of Infectious Diseases May 1988We used a bioassay to measure pentamidine concentrations in autopsy specimens from 22 patients with AIDS. Patients received pentamidine isethionate (approximately 4... (Comparative Study)
Comparative Study
We used a bioassay to measure pentamidine concentrations in autopsy specimens from 22 patients with AIDS. Patients received pentamidine isethionate (approximately 4 mg/kg per day) parenterally for Pneumocystis carinii pneumonia; one received monthly prophylaxis. We found that lung levels of 30 micrograms/g were achieved only after the fifth dose; tissue accumulation was usually greater in the liver, kidney, adrenal, and spleen than in the lung; detectable levels were present in some tissues as late as one year after the last dose; and low but detectable levels were present in the brain of six of 17 patients. Two patients had no detectable lung levels after two days of therapy; one had a level of 17.5 micrograms/g after four doses, and two had levels of 30 micrograms/g after five doses. A more rapid and effective method of delivery, such as aerosol, should achieve higher concentrations earlier. Because pentamidine persists in lung tissue over days to weeks, daily administration may not be necessary.
Topics: Acquired Immunodeficiency Syndrome; Adrenal Glands; Amidines; Brain; Humans; Kidney; Liver; Lung; Pentamidine; Pneumonia, Pneumocystis; Spleen; Tissue Distribution
PubMed: 3258901
DOI: 10.1093/infdis/157.5.985 -
Annals of Internal Medicine Sep 1985
Topics: Amidines; Humans; Hypotension; Infusions, Parenteral; Injections, Intramuscular; Injections, Intravenous; Pentamidine
PubMed: 4026103
DOI: 10.7326/0003-4819-103-3-480_1 -
Drug Intelligence & Clinical Pharmacy May 1987
Comparative Study
Topics: Amidines; Humans; Hypotension; Monitoring, Physiologic; Pentamidine; Pneumonia, Pneumocystis
PubMed: 3495422
DOI: 10.1177/106002808702100522 -
Thorax Mar 1993Nebulised pentamidine is effective for preventing Pneumocystis carinii pneumonia in adults with acquired immunodeficiency syndrome. The nebuliser dose required to...
BACKGROUND
Nebulised pentamidine is effective for preventing Pneumocystis carinii pneumonia in adults with acquired immunodeficiency syndrome. The nebuliser dose required to produce equivalent lung concentrations of pentamidine in children is unknown. This study was performed to measure pulmonary pentamidine deposition in children and to relate this to age, ventilation pattern, and body size.
METHODS
Nebulised pentamidine (50 mg in 6 ml saline) was administered to 12 children (including one with lymphocytic interstitial pneumonitis) and to six adults with human immunodeficiency virus infection using a Respirgard II nebuliser. Technetium-99m labeled colloidal human serum albumin was used as an indirect marker for pentamidine and deposition in the lungs was detected by a gamma camera.
RESULTS
Absolute deposition of pentamidine was not related to age, height, weight, spirometry, or ventilation characteristics. Deposition, as a mean (SD) percentage of nebuliser output, was similar in children aged 8-11 years (5.5(2.4)%), teenagers aged 12-15 years (7.2(2.2)%) and adults (7.1(2.6)%). Aerosol concentration within the lungs (% nebuliser output deposited/predicted total lung capacity) was therefore higher in children (1.9(1.5)%/1) and teenagers (1.9(0.7)%/1) than in adults (1.0(0.7%)/1), and was negatively correlated with height (r = -0.69) and weight (r = -0.50). Deposition of aerosol in the region of the large central airways was particularly marked in children. Small reductions in forced expiratory volume in one second and forced vital capacity after treatment did not differ significantly between adults and children and visual analogue scores of subjective adverse effects did not vary with age.
CONCLUSIONS
These results suggest that children probably require lower nebuliser pentamidine doses to produce lung pentamidine concentrations equivalent to those found to be effective for preventing P carinii pneumonia in adults using the Respirgard II nebuliser.
Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Age Factors; Body Constitution; Child; Drug Administration Schedule; Humans; Lung; Male; Nebulizers and Vaporizers; Pentamidine; Pneumonia, Pneumocystis; Respiration; Respiratory Function Tests
PubMed: 8497819
DOI: 10.1136/thx.48.3.220 -
Chest Jan 1994Recent studies have suggested that failure of pentamidine prophylaxis against Pneumocystis carinii pneumonia (PCP) may be due to reduced deposition of pentamidine in the...
Recent studies have suggested that failure of pentamidine prophylaxis against Pneumocystis carinii pneumonia (PCP) may be due to reduced deposition of pentamidine in the upper lobes. In this study, we performed bronchoalveolar lavage from the apical segment of the upper lobe and the middle lobe in 51 HIV-positive patients, all of whom were receiving prophylaxis with aerosolized pentamidine, who had presented with acute respiratory symptoms. Lavage fluid from each lobe was assayed for pentamidine using high-performance liquid chromatography (HPLC). The number of clusters of P carinii were counted after staining with a Wright-Giemsa stain. The patients were subclassified as PCP-positive (32 patients) and PCP-negative (19 patients) on the basis of the presence/absence of P carinii clusters in their BAL fluid. The concentration of pentamidine in the upper lobe compared with the middle lobe was no different (using paired Student's t tests) for either PCP-positive patients or PCP-negative patients. In comparing the positive with the negative subjects, using unpaired Student's t test, there was no difference in the concentration of pentamidine in the upper lobe or the middle lobe. For PCP-positive patients, the numbers of P carinii clusters were on average higher in the upper lobes (mean +/- SD: upper = 14.9 +/- 16.6, middle 7.5 +/- 10.8, p = 0.013, paired Student's t test), but there was no correlation between lobar P carinii cluster counts and pentamidine levels. We conclude that the absence of a relationship between cluster count and pentamidine level, the similarity in regional pentamidine levels between upper and middle lobes, as well as the similarity in pentamidine levels between the PCP-positive and PCP-negative groups indicate that the regional dose of pentamidine is not the determining factor as to whether aerosolized pentamidine prophylaxis will succeed or fail.
Topics: Adult; Aerosols; Bronchoalveolar Lavage Fluid; Chromatography, High Pressure Liquid; Colony Count, Microbial; Follow-Up Studies; HIV Seropositivity; Humans; Lung; Nebulizers and Vaporizers; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Time Factors
PubMed: 8275783
DOI: 10.1378/chest.105.1.53 -
Chest Oct 1989
Topics: Acquired Immunodeficiency Syndrome; Aerosols; Humans; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis
PubMed: 2791660
DOI: 10.1378/chest.96.4.713