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B M Anene - One of the best experts on this subject based on the ideXlab platform.
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COMPARATIVE PROPHYLACTIC EFFICACY OF Pentamidine AND ISOMETAMIDIUM IN MICE EXPERIMENTALLY-INFECTED WITH Trypanosoma brucei brucei
Philippine Journal of Veterinary and Animal Sciences, 2012Co-Authors: R. Nwoha, B M AneneAbstract:The development of resistance in trypanosomes to commonly-used trypanocides has an important implication in the chemotherapy and prophylaxis of both human and animal trypanosomosis. This study compared the prophylactic activity of Pentamidine Isethionate and isometamidium chloride in mice experimentally-infected with Trypanosoma brucei brucei. The 96 mice were divided into four groups with 24 animals each: a) Group I - untreated control group; b) Group II - treated with Pentamidine Isethionate at 4 mg/kg body weight for 3 alternate days; c) Group III - treated with Pentamidine Isethionate at 8 mg/kg body weight for 3 alternate days; and d) Group IV - treated once with isometamidium chloride at 1 mg/kg body weight. Thereafter, three mice from each group were infected intraperitoneally with T. brucei brucei at weekly intervals and monitored for parasitaemia. The entire control group was positive for T. brucei brucei by day 6 post infection. Parasitaemia was recorded in Group II at 3 weeks post infection, at 4 weeks in Group III and at 8 weeks in Group IV. Group IV had the highest survival rate followed by Group III. The results showed that isometamidium chloride provides better prophylaxis than Pentamidine Isethionate. Keywords: isometamidium chloride, mice, Pentamidine Isethionate, trypanosome
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comparative efficacy assessment of Pentamidine Isethionate and diminazene aceturate in the chemotherapy of trypanosoma brucei brucei infection in dogs
Veterinary Parasitology, 2008Co-Authors: P O Akpa, R C Ezeokonkwo, B M AneneAbstract:Abstract The chemotherapeutic efficacy of diminazene aceturate (Berenil®) – a standard veterinary trypanocide and Pentamidine Isethionate (PMI) – a human trypanocide was compared in dogs experimentally infected with Trypanosoma brucei brucei. Also, the activities of the drugs on some serum liver enzymes were evaluated before and after treatment to ascertain the relative safety of the drugs. Fifteen local dogs (mongrels) were used for the study. Three of the dogs were uninfected controls, and twelve were infected with a stock of T. brucei brucei. Three of the infected dogs were untreated controls, three were given diminazene aceturate (DA) at 7 mg/kg body weight intramuscularly (i/m), another three received Pentamidine Isethionate (PMI) at 4 mg/kg i/m on days 14, 17, 19, 27, 29, and 31 post infection (PI) and the remaining three dogs were also given same dose of PMI on days 14, 16, 18, 20, 22, 24 and 26 PI. Both trypanocides effectively cleared the parasites from the blood of the infected treated dogs. However, the infection subsequently relapsed at day 42 PI in one of the dogs in the DA treated group which later died at day 70 PI. Relapse infection was not recorded with the PMI treated groups although two dogs died in the PMI treated group II (treatment at days 14, 17, 19, 27, 29, and 31 PI) without showing relapsed parasitaemia. The packed cell volume (PCV), red blood cell (RBC) count, and haemoglobin (Hb) level which decreased significantly following infection, were reversed by the trypanocidal treatment. The reversal in the red cell values was faster in the PMI treated groups than in the DA treated group. The serum alkaline phosphate (SAP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels increased following infection and drug administration. The increase in the enzyme levels was greater in the DA treated groups than PMI treated groups. It was thus concluded that PMI given at 4 mg/kg i/m at days 14, 16, 18, 20, 22, 24, and 26 PI constituted a safe and efficient trypanocide and exhibited a superior trypanocidal action than DA in T. brucei brucei infected dogs.
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A diminazene-resistant strain of Trypanosoma brucei brucei isolated from a dog is cross-resistant to Pentamidine in experimentally infected albino rats
Parasitology, 2005Co-Authors: B M Anene, R C Ezeokonkwo, T. I. Mmesirionye, J. N. A. Tettey, J. M. Brock, M. P. Barrett, H. P. De KoningAbstract:Trypanosomosis is a major cause of mortality for dogs in Nigeria and treatment with diminazene aceturate has steadily become less effective, either as a result of low quality of the locally available diminazene preparations or of drug resistance. To investigate these alternatives, samples of locally obtained drugs were analysed for diminazene aceturate content and a strain of Trypanosoma brucei brucei was isolated from a diminazene-refractory dog in Nsukka, south-eastern Nigeria, and used to infect albino rats. The quality of diminazene aceturate-based preparations was variable, with two preparations containing less than 95% of the stated active compound. Rats infected with T. brucei isolated from the dog were treated 7 and 10 days after infection either with 7 mg/kg diminazene aceturate (intraperitoneally, once) or with 4 mg/kg Pentamidine Isethionate (intramuscularly, 7 consecutive days). Relapse rates were 100% for both trypanocides in the groups of rat treated 10 days post-infection, and 83% and 50% of rats treated 7 days after infection relapsed to diminazene aceturate and Pentamidine Isethionate, respectively. Careful consideration of physiological parameters showed that Pentamidine was only marginally superior to diminazene aceturate as applied in this study. It was concluded that dogs in Nigeria are infected with genuinely diminazene aceturate-resistant trypanosomes that appear to be cross-resistant to Pentamidine Isethionate.
Anette Chrusciak Talhari - One of the best experts on this subject based on the ideXlab platform.
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An open label randomized clinical trial comparing the safety and effectiveness of one, two or three weekly Pentamidine Isethionate doses (seven milligrams per kilogram) in the treatment of cutaneous leishmaniasis in the Amazon Region.
PLOS Neglected Tropical Diseases, 2018Co-Authors: Ellen Priscilla Nunes Gadelha, Rajendranath Ramasawmy, Bruna Da Costa Oliveira, Nágila Morais Rocha, Jorge Augusto De Oliveira Guerra, George Allan Villarouco Da Silva, Tirza Gabrielle Ramos De Mesquita, Carolina Chrusciak Talhari Cortez, Anette Chrusciak TalhariAbstract:Background American Cutaneous Leishmaniasis (ACL), a vector borne disease, is caused by various species of Leishmania and in the Amazonas, Leishmania guyanensis is predominant. The recommended drugs for treatment of cutaneous leishmaniasis (CL) in Brazil are pentavalent antimonials, Pentamidine Isethionate (PI) and amphotericin B. Pentamidine was initially used as metanolsulfonate or mesylate (Lomidine) at a dose of 4 mg/kg/daily, containing 2.3mg of base. This drug was withdrawn from the market in the eighties, and currently is available as PI. The PI dose required to achieve an equivalent dose of Pentamidine base is 7 mg/kg, rather than the 4 mg/kg that is currently recommended in Brazil. Objectives The aim of this study was to evaluate the efficacy and safety of PI in a single dose, two or three doses of 7 mg/kg body weight, intramuscularly, with an interval of seven days between each dose. Materials and methods This study was conducted as a controlled, randomized, open–label clinical trial for a total number of 159 patients with CL. Individuals aged 16–64 years with one to six lesions of confirmed CL based on amastigotes visualization in direct examination of Giemsa stained of dermal scraping from the border of the lesion with no previous treatment for CL and no abnormal values for liver enzymes were eligible to participate in the study. Patients with history of diabetes, cardiac, renal, and hepatic disease as well as pregnant women were excluded. Cure was defined as complete healing in the diameters of the ulcers and lesions skin six months after the end of the treatment. Results From November 2013 to December 2015, 159 patients were screened and allocated in three groups for treatment with PI: i) 53 patients were treated with a single dose intramuscularly injection of 7 mg/kg body weight; ii) 53 received two doses of 7 mg/kg within an interval of seven days; and iii) 53 were treated with three doses of 7mg/kg with an interval of seven days between each dose. In 120 patients, L. guyanensis was identified. A cure rate of 45%, 81.1% and 96.2% were observed in the first, second and third group, respectively. The cure in the three PI dose group was higher compared to the single-dose (p
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an open label randomized clinical trial comparing the safety and effectiveness of one two or three weekly Pentamidine Isethionate doses seven milligrams per kilogram in the treatment of cutaneous leishmaniasis in the amazon region
PLOS Neglected Tropical Diseases, 2018Co-Authors: Ellen Priscilla Nunes Gadelha, Rajendranath Ramasawmy, Bruna Da Costa Oliveira, Nágila Morais Rocha, Jorge Augusto De Oliveira Guerra, George Allan Villarouco Da Silva, Tirza Gabrielle Ramos De Mesquita, Carolina Chrusciak Talhari Cortez, Anette Chrusciak TalhariAbstract:Background American Cutaneous Leishmaniasis (ACL), a vector borne disease, is caused by various species of Leishmania and in the Amazonas, Leishmania guyanensis is predominant. The recommended drugs for treatment of cutaneous leishmaniasis (CL) in Brazil are pentavalent antimonials, Pentamidine Isethionate (PI) and amphotericin B. Pentamidine was initially used as metanolsulfonate or mesylate (Lomidine) at a dose of 4 mg/kg/daily, containing 2.3mg of base. This drug was withdrawn from the market in the eighties, and currently is available as PI. The PI dose required to achieve an equivalent dose of Pentamidine base is 7 mg/kg, rather than the 4 mg/kg that is currently recommended in Brazil. Objectives The aim of this study was to evaluate the efficacy and safety of PI in a single dose, two or three doses of 7 mg/kg body weight, intramuscularly, with an interval of seven days between each dose. Materials and methods This study was conducted as a controlled, randomized, open–label clinical trial for a total number of 159 patients with CL. Individuals aged 16–64 years with one to six lesions of confirmed CL based on amastigotes visualization in direct examination of Giemsa stained of dermal scraping from the border of the lesion with no previous treatment for CL and no abnormal values for liver enzymes were eligible to participate in the study. Patients with history of diabetes, cardiac, renal, and hepatic disease as well as pregnant women were excluded. Cure was defined as complete healing in the diameters of the ulcers and lesions skin six months after the end of the treatment. Results From November 2013 to December 2015, 159 patients were screened and allocated in three groups for treatment with PI: i) 53 patients were treated with a single dose intramuscularly injection of 7 mg/kg body weight; ii) 53 received two doses of 7 mg/kg within an interval of seven days; and iii) 53 were treated with three doses of 7mg/kg with an interval of seven days between each dose. In 120 patients, L. guyanensis was identified. A cure rate of 45%, 81.1% and 96.2% were observed in the first, second and third group, respectively. The cure in the three PI dose group was higher compared to the single-dose (p<0.0001) and two-dose groups (p = 0.03). No serious adverse events occurred. Conclusion The present study shows that PI is a safe drug and its efficacy varied with the number of doses. The administration of PI in patients with ACL, predominantly caused by L. guyanensis, was mostly efficient in three or two doses of 7 mg/kg. Trial registration ClinicalTrials.gov NCT02919605
Raj Suryanarayanan - One of the best experts on this subject based on the ideXlab platform.
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physical characterization of Pentamidine Isethionate during freeze drying relevance to development of stable lyophilized product
Journal of Pharmaceutical Sciences, 2012Co-Authors: Prakash Sundaramurthi, Michael R Burcusa, Raj SuryanarayananAbstract:ABSTRACT The purpose of this study was to perform physical characterization of Pentamidine Isethionate (PI) in frozen and freeze-dried systems and to monitor the phase behavior during all the stages of freeze-drying. Frozen aqueous PI solutions as well as the final lyophiles were characterized by differential scanning calorimetry and X-ray diffractometry. The effect of cosolutes, cosolvents, and processing conditions on the PI crystallization behavior during freeze-drying was evaluated. In frozen aqueous solutions, irrespective of the cooling rate and the initial solute concentration, PI readily crystallized as a trihydrate (C 19 H 24 N 4 O 2 ·3H 2 O). It dehydrated to a poorly crystalline anhydrate upon drying at 100 mTorr. The presence of a readily crystallizing cosolute or an organic cosolvent did not influence the physical form of PI in the final lyophile. On the contrary, even in the absence of cosolutes and cosolvents, the crystalline trihydrate was retained when the chamber pressure was increased to 500 mTorr. By altering the drying conditions, it was possible to obtain either a crystalline trihydrate or a poorly crystalline anhydrate. The stability of PI is dependent on its physical form and only the amorphous PI undergoes discoloration. The PI stability can be enhanced by retaining it in a crystalline state in the lyophile. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:1732–1743, 2012
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Physical Characterization of Pentamidine Isethionate during Freeze-Drying—Relevance to development of Stable Lyophilized Product
Journal of Pharmaceutical Sciences, 2012Co-Authors: Prakash Sundaramurthi, Michael R Burcusa, Raj SuryanarayananAbstract:ABSTRACT The purpose of this study was to perform physical characterization of Pentamidine Isethionate (PI) in frozen and freeze-dried systems and to monitor the phase behavior during all the stages of freeze-drying. Frozen aqueous PI solutions as well as the final lyophiles were characterized by differential scanning calorimetry and X-ray diffractometry. The effect of cosolutes, cosolvents, and processing conditions on the PI crystallization behavior during freeze-drying was evaluated. In frozen aqueous solutions, irrespective of the cooling rate and the initial solute concentration, PI readily crystallized as a trihydrate (C 19 H 24 N 4 O 2 ·3H 2 O). It dehydrated to a poorly crystalline anhydrate upon drying at 100 mTorr. The presence of a readily crystallizing cosolute or an organic cosolvent did not influence the physical form of PI in the final lyophile. On the contrary, even in the absence of cosolutes and cosolvents, the crystalline trihydrate was retained when the chamber pressure was increased to 500 mTorr. By altering the drying conditions, it was possible to obtain either a crystalline trihydrate or a poorly crystalline anhydrate. The stability of PI is dependent on its physical form and only the amorphous PI undergoes discoloration. The PI stability can be enhanced by retaining it in a crystalline state in the lyophile. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:1732–1743, 2012
N T Bateman - One of the best experts on this subject based on the ideXlab platform.
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pulmonary deposition of nebulised Pentamidine Isethionate effect of nebuliser type dose and volume of fill
Thorax, 1990Co-Authors: Michael Odoherty, Shl Thomas, Clive P. Page, T. O. Nunan, C S Bradbeer, N T BatemanAbstract:An estimate of the absolute pulmonary deposition of nebulised Pentamidine Isethionate was obtained in nine patients with AIDS. Two nebuliser systems were compared, System 22 Mizer (Medic-Aid) and Respirgard II (Marquest), with 50 and 150 mg doses of Pentamidine in a 3 ml solution driven by an air flow of 6 l/min with the patient in the sitting position. The 50 mg Pentamidine dose was repeated with a 6 ml fill with both devices. The nebuliser cloud was labelled with technetium-99m human serum albumin (Ventocol) and lung deposition was measured with a gamma camera. Of the two nebulisers studied, System 22 Mizer delivered more drug to the lungs as a whole and to each individual lung region, including the peripheral and upper zones. For the 50 mg dose the mean (SEM) total pulmonary deposition with the 3 and the 6 ml fill respectively was 2.63 (0.34) and 3.71 (0.41) mg for the System 22 Mizer and 1.37 (0.26) and 1.45 (0.18) mg for the Respirgard II. For the 150 mg dose the System 22 Mizer delivered 7.16 (1.02) mg and the Respirgard II 4.34 (0.57) mg. Increasing the volume of fill from 3 to 6 ml increased pulmonary deposition with System 22 Mizer, and this was related to an increase in nebuliser output. Neither pulmonary deposition nor nebuliser output was increased by using a 6 ml solution in the Respirgard II. Increasing the volume of fill prolonged the time required for nebulisation with both nebulisers. The System 22 Mizer produced more nonpulmonary (gastric and oropharyngeal) deposition of drug, more frequent local adverse effects (cough, burning in the throat, and a metallic taste), and small reductions in lung function, particularly with the 150 mg Pentamidine dose. Thus nebuliser type, volume of fill, and nebuliser dose affect the pulmonary deposition of Pentamidine. A 300 mg dose of Pentamidine via a Respirgard II is generally recommended as providing effective prophylaxis; our results suggest that similar pulmonary deposition can be produced with System 22 Mizer and 150 mg Pentamidine. A clinical trial would be needed to show whether this regimen provides similar prophylactic benefit.
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Pulmonary deposition ofnebulised Pentamidine Isethionate: effect ofnebuliser type,dose, and volume offill
1990Co-Authors: Michael Doherty, Caroline Bradbeer, N T BatemanAbstract:estimate oftheabsolute pulmonary deposition of nebulised Pentamidine Isethionate wasobtained inninepatients withAIDS.Two nebuliser systemswere compared, System22Mizer(Medic-Aid) andRespirgard II(Marquest), with50 and150mg dosesofPentamidine ina 3ml solution drivenbyanairflowof6 l/min withthepatient inthesitting posi- tion.The 50mg Pentamidine dosewas repeated witha 6ml fillwithboth devices. Thenebuliser cloudwaslabelled withtechnetium-99m humanserumal- bumin (Ventocol) andlungdeposition wasmeasuredwithagamma camera.Of thetwonebulisers studied, System22 Mizerdelivered moredrugtothelungs asa wholeandtoeachindividual lung region, including theperipheral and upperzones.Forthe50mg dosethe mean(SEM)total pulmonary deposition withthe3andthe6ml fill respectively
Michael Odoherty - One of the best experts on this subject based on the ideXlab platform.
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preparation and stability of a radioiodinated Pentamidine Isethionate analog
International Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes, 1992Co-Authors: Philip J. Blower, Claire M Smith, Raymond J Smith, Gareth E Moores, Michael OdohertyAbstract:Abstract IodoPentamidine Isethionate was heated for 70 min with [I-123]- or [I-125]-sodium iodide and ammonium sulphate in the absence of solvent at 140°C. The product, [I-123]- or [I-125]-iodoPentamidine Isethionate, was purified by ion exchange chromatography. It was stable at room temperature in aqueous solution over several days, in human blood in vitro for at least 24 h (showing no binding to either cells or proteins), in urine over at least 15 h, and during nebulization in both ultrasonic and jet nebulizers.
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pulmonary deposition of nebulised Pentamidine Isethionate effect of nebuliser type dose and volume of fill
Thorax, 1990Co-Authors: Michael Odoherty, Shl Thomas, Clive P. Page, T. O. Nunan, C S Bradbeer, N T BatemanAbstract:An estimate of the absolute pulmonary deposition of nebulised Pentamidine Isethionate was obtained in nine patients with AIDS. Two nebuliser systems were compared, System 22 Mizer (Medic-Aid) and Respirgard II (Marquest), with 50 and 150 mg doses of Pentamidine in a 3 ml solution driven by an air flow of 6 l/min with the patient in the sitting position. The 50 mg Pentamidine dose was repeated with a 6 ml fill with both devices. The nebuliser cloud was labelled with technetium-99m human serum albumin (Ventocol) and lung deposition was measured with a gamma camera. Of the two nebulisers studied, System 22 Mizer delivered more drug to the lungs as a whole and to each individual lung region, including the peripheral and upper zones. For the 50 mg dose the mean (SEM) total pulmonary deposition with the 3 and the 6 ml fill respectively was 2.63 (0.34) and 3.71 (0.41) mg for the System 22 Mizer and 1.37 (0.26) and 1.45 (0.18) mg for the Respirgard II. For the 150 mg dose the System 22 Mizer delivered 7.16 (1.02) mg and the Respirgard II 4.34 (0.57) mg. Increasing the volume of fill from 3 to 6 ml increased pulmonary deposition with System 22 Mizer, and this was related to an increase in nebuliser output. Neither pulmonary deposition nor nebuliser output was increased by using a 6 ml solution in the Respirgard II. Increasing the volume of fill prolonged the time required for nebulisation with both nebulisers. The System 22 Mizer produced more nonpulmonary (gastric and oropharyngeal) deposition of drug, more frequent local adverse effects (cough, burning in the throat, and a metallic taste), and small reductions in lung function, particularly with the 150 mg Pentamidine dose. Thus nebuliser type, volume of fill, and nebuliser dose affect the pulmonary deposition of Pentamidine. A 300 mg dose of Pentamidine via a Respirgard II is generally recommended as providing effective prophylaxis; our results suggest that similar pulmonary deposition can be produced with System 22 Mizer and 150 mg Pentamidine. A clinical trial would be needed to show whether this regimen provides similar prophylactic benefit.