Introduction: Enterococcus faecalis is a frequent etiologic agent of invasive infections in hospi... more Introduction: Enterococcus faecalis is a frequent etiologic agent of invasive infections in hospitalized patients. The aim of this study was to analyze clinical and microbiological features of bacteremia caused by E. faecalis. Methodology: Between 2011 and 2013, significant bacteremia caused by E. faecalis in hospitalized patients was studied. Patient characteristics, comorbid conditions, and 14-day mortality were recorded. Virulence genes esp, gelE, and cylA; opsonophagocytosis resistance; resistance to bactericidal effect of normal serum; beta lactamase production; and susceptibility to ampicillin, vancomycin, teicoplanin, gentamicin, and streptomycin were investigated. Results: E. faecalis strains were recovered from 33 bacteremic patients. Polymicrobial bacteremia was diagnosed in 2 patients; 10 patients died. Virulence genes were found in strains from both deceased patients and survivors. Sources of bacteremia included urinary tract infections (36.4%), vascular catheters (15.1%), abscesses (9.1%), and unknown (48.5%). Underlying diseases included cancer (30.3%), diabetes (36.4%), cirrhosis (6.1%), renal (36.4%), and chronic obstructive pulmonary disease (2.0%). Co-morbidities included alcohol use (26.1%); glucocorticoid therapy (19.0%); prior antibiotic therapy (60.6%); and central venous (21.2%), arterial (12.1%), and urinary (63.6%) catheters. Also, 57.6% of patients came from the intensive care unit (ICU); 33.3% had mechanical ventilation. Significant mortality-associated conditions included polymicrobial bacteremia, oncological disease, APACHE II score ≥ 20, ICU stay, renal disease, central venous catheter, and mechanical ventilation. Conclusions: Outcome of patients was associated with their status and not with the presence of virulence genes in E. faecalis strains. A significant percentage of bacteremia had undetermined origin. An alternate origin may be the gastrointestinal tract, through translocation.
Resistant Gram-positive bacteria are causing increasing concern in clinical practice. This work i... more Resistant Gram-positive bacteria are causing increasing concern in clinical practice. This work investigated the efficacy of AP-CECT7121 (an antimicrobial peptide isolated from an environmental strain of Enterococcus faecalis CECT7121) against various pathogenic Gram-positive bacteria. Strains were isolated from intensive care unit patients unresponsive to standard antibiotic treatments. Inhibitory activity of AP-CECT7121 was assessed using the agar-well diffusion method. The most resistant isolates from each species screened (Enterococcus faecium, Enterococcus faecalis,Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Clostridium perfringens and Clostridium difficile) were further examined in time-killing curve studies. These bactericidal kinetic experiments demonstrated a rapid killing effect with no viable bacteria being detected within 30 and 90 min for enterococcal and streptococcal strains and 180 min for community-acquired methicillin-resistant S. aureus and C. perfringens: viable counts for C. difficile were threefold decreased after 90 min. AP-CECT7121 may provide a novel strategy for treating potentially fatal clinical infections in hospitalized patients.
Argentina Biomedical Science has been historically strong. The development of Human and Veterinar... more Argentina Biomedical Science has been historically strong. The development of Human and Veterinary Pharmacology in our country as a pivotal discipline has been acknowledged worldwide because of the quality of its contributions. Argentinean Society of Experimental Pharmacology (SAFE) is a non- profit association whose research fields include Experimental and Clinical Pharmacology. SAFE main goals are described as follow: a) To meet active researchers for studying concerns regarding Experimental and Clinical Pharmacology, b) To launch an initiative for development of the discipline in mainly our country and other collaborative countries worldwide, c) To spread the pharmacological know-how obtained from different research teams, d) To strengthen relations between pharmacologists, e) To facilitate the presentation and discussion of scientific papers. This current article shows the SAFÉs more important scientific contribution to pharmacology through its former research scientists to the present.
The Journal of Infection in Developing Countries, 2015
Enterococcus faecalis is a frequent etiologic agent of invasive infections in hospitalized patien... more Enterococcus faecalis is a frequent etiologic agent of invasive infections in hospitalized patients. The aim of this study was to analyze clinical and microbiological features of bacteremia caused by E. faecalis. Between 2011 and 2013, significant bacteremia caused by E. faecalis in hospitalized patients was studied. Patient characteristics, comorbid conditions, and 14-day mortality were recorded. Virulence genes esp, gelE, and cylA; opsonophagocytosis resistance; resistance to bactericidal effect of normal serum; beta lactamase production; and susceptibility to ampicillin, vancomycin, teicoplanin, gentamicin, and streptomycin were investigated. E. faecalis strains were recovered from 33 bacteremic patients. Polymicrobial bacteremia was diagnosed in 2 patients; 10 patients died. Virulence genes were found in strains from both deceased patients and survivors. Sources of bacteremia included urinary tract infections (36.4%), vascular catheters (15.1%), abscesses (9.1%), and unknown (48.5%). Underlying diseases included cancer (30.3%), diabetes (36.4%), cirrhosis (6.1%), renal (36.4%), and chronic obstructive pulmonary disease (2.0%). Co-morbidities included alcohol use (26.1%); glucocorticoid therapy (19.0%); prior antibiotic therapy (60.6%); and central venous (21.2%), arterial (12.1%), and urinary (63.6%) catheters. Also, 57.6% of patients came from the intensive care unit (ICU); 33.3% had mechanical ventilation. Significant mortality-associated conditions included polymicrobial bacteremia, oncological disease, APACHE II score ≤ 20, ICU stay, renal disease, central venous catheter, and mechanical ventilation. Outcome of patients was associated with their status and not with the presence of virulence genes in E. faecalis strains. A significant percentage of bacteremia had undetermined origin. An alternate origin may be the gastrointestinal tract, through translocation.
Therapeutic failures attributed to medical management of cystic echinococcosis (CE) with albendaz... more Therapeutic failures attributed to medical management of cystic echinococcosis (CE) with albendazole (ABZ) have been primarily linked to the poor drug absorption rate resulting in low drug level in plasma and hydatid cysts. Lipid nanocapsules (LNCs) represent nanocarriers designed to encapsulate lipophilic drugs, such as ABZ. The goals of the current work were: (i) to characterize the plasma and cyst drug exposure after the administration of ABZ as ABZ-LNCs or ABZ suspension (ABZ-SUSP) in mice infected with Echinococcus granulosus, and ii) to compare the clinical efficacies of both ABZ formulations. Enhanced ABZ sulphoxide (ABZ-SO) concentration profiles were obtained in plasma and cysts from ABZ-LNC treated animals. ABZSO exposure (AUC0-LOQ) was significantly higher in plasma and cyst after the ABZ-LNC treatments, both orally and subcutaneously, compared to that observed after oral administration of ABZ-SUSP. Additionally, ABZSO concentrations measured in cysts from ABZ-LNC treated mice were 1.7-fold higher than those detected in plasma. This enhanced drug availability correlated with an increased efficacy against secondary CE in mice observed for the ABZ-LNCs, while ABZ-SUSP did not reach differences with the untreated control group. This new pharmacotechnically-based strategy could be a potential alternative to improve the treatment of human CE.
The current chemotherapy of cystic echinococcosis (CE) is mainly based on the use of albendazole,... more The current chemotherapy of cystic echinococcosis (CE) is mainly based on the use of albendazole, and the results have been shown to be highly variable. Thus, new and more efficient treatment options are urgently needed. The goals of the current study were: (a) to compare the ex vivo activity of flubendazole (FLBZ) and nitazoxanide (NTZ), given either separately or co-administered, against Echinococcus granulosus protoscoleces and cysts, (b) to characterize the plasma disposition kinetics of FLBZ administered alone or combined with NTZ in mice; (c) to compare the in vivo activity of FLBZ and NTZ (either each alone or as a combined treatment) against secondary CE developed in mice. Ex vivo drug activity study: E. granulosus protoscoleces and cysts were incubated either with FLBZ, NTZ, or the FLBZ-NTZ combination. Protoscoleces and cyst viability was monitored by the methylene blue exclusion test and scanning electron microscopy (SEM). Pharmacokinetic study: Balb/C mice received FLBZ (5mg/kg) orally either alone or co-administered with NTZ (100mg/kg). Blood samples were collected up to 12h post treatment and plasma analyzed for FLBZ/metabolites by HPLC. Clinical Efficacy study: following secondary infection, meaning i.p. injection of 1500 E. granulosus protoscoleces/animal (n=40), the both drugs were administered by intragastric inoculation on a daily basis for a period of 25 days. Balb/C mice received FLBZ (5mg/kg, twice a day) alone, NTZ (100mg/kg, once daily) alone or a combination of both molecules (FLBZ, 5mg/kg twice a day and NTZ, 100mg/kg, once daily). Ten untreated animals were used as a control. All animals were killed and the weight of the cysts collected from each animal was recorded. The presence of NTZ did not markedly affect the FLBZ kinetic parameters in mice. FLBZ alone or combined with NTZ induced a reduction (P<0.05) of cyst weight in comparison to the untreated control and NTZ-treated treated mice. The data obtained here indicate that NTZ did not affect hydatid cyst development in mice. Conversely, FLBZ shows an excellent efficacy against CE.
The pharmacokinetics of tylosin were compared in cattle (Bos taurus) and buffaloes (Bubalus bubal... more The pharmacokinetics of tylosin were compared in cattle (Bos taurus) and buffaloes (Bubalus bubalis). Six animals received each a single dose of 10 mg/kg of tylosin tartrate by the intramuscular route. The serum concentration (Cmax) and the volume of distribution (Vd) presented significant differences between the two species. Cmax was 0.40 +/- 0.046 microg/ml for buffaloes and 0.64 +/- 0.068 microg/ml for cattle. Vd was 1.91 +/- 0.12 L/kg and 1.33 +/- 0.09 L/kg for buffaloes and cattle, respectively. However, as the present study did not show considerable differences in the pharmacokinetics of tylosin in buffaloes and cattle, similar dosage regimes of this drug can be recommended for both species.
The current experiments compare the pattern of ex vivo uptake (diffusion) of albendazole (ABZ) an... more The current experiments compare the pattern of ex vivo uptake (diffusion) of albendazole (ABZ) and albendazole sulfoxide (ABZSO) by Ascaris suum and Fasciola hepatica. Specimens of A. suum and F. hepatica were collected from untreated animals (pigs and sheep, respectively) and incubated with either ABZ or ABZSO for different time periods (5-180 min). After incubation. the parasite material was analysed by HPLC to quantify the amount of ABZ and/or ABZSO. The parent drug and its active ABZSO metabolite were recovered from the parasites after ex vivo incubation for different time periods throughout the assay. Total drug availability in A. suum, expressed as area under the concentration versus time curve (AUC) over 180 min of incubation, was significantly greater (P<0.05) for ABZ parent drug (AUC = 4.19 +/- 0.59 microg x h xg(-1)) compared with the more polar ABZSO metabolite (AUC = 0.25 +/- 0.01 micro x h x g(-1)). Similar results were observed after the incubation of both molecules...
We evaluated the comparative plasma and abomasal fluid disposition kinetics of albendazole (ABZ) ... more We evaluated the comparative plasma and abomasal fluid disposition kinetics of albendazole (ABZ) and its metabolites in calves either grazing on pasture or fed a grain-based concentrate diet. Six male Holstein calves (weight 180 to 200 kg) were allowed to graze on lush pasture for three weeks before intraruminal administration of ABZ at 10 mg kg-1(pasture group). After a three-week wash-out period, the same animals were housed and fed on a grain-based concentrate diet for three weeks prior to receiving the same ABZ treatment (concentrate group). Jugular blood and abomasal fluid samples were collected over 120 hours post-treatment. Plasma and abomasal fluid samples were analysed by high performance liquid chromatography (HPLC). The digesta transit time was measured using cobalt (Co) as a fluid marker; abomasal fluid and faecal samples were collected and Co concentrations measured by atomic absorption spectrophotometry. Complementary studies of the in vitro dissolution of ABZ particle...
The influence of diet on the disposition kinetics of albendazole (ABZ) and its metabolites in pig... more The influence of diet on the disposition kinetics of albendazole (ABZ) and its metabolites in pigs was investigated. ABZ was administered orally at 10 mg kg-1 to pigs fed either a commercially produced 35 per cent protein/grain concentrate diet (concentrate group), a whey-based diet supplemented with corn grain (whey/grain group) or grazed on pasture (pasture group). Blood samples were taken serially for 96 hours and plasma was analysed by high performance liquid chromatography (HPLC) for ABZ, ABZ sulphoxide (ABZSO), ABZ sulphone (ABZSO2) and amino-ABZSO2 (NH2ABZSO2). ABZ was not detected in plasma at any time after the treatment, and ABZSO and ABZSO2 were the main metabolites detected between 0.5 and 30 to 48 hours after treatment in all the experimental animals. Low concentrations of the NH2ABZSO2 metabolite were found in plasma between 18 and 36 hours after the administration of ABZ to all the groups of pigs. The pharmacokinetic behaviour of the ABZ metabolites in pigs fed either the concentrate of the whey/concentrate diet was substantially different from that observed in pigs grazing on pasture. The peak concentration (C(max)) and areas under the concentration-time curves (AUC) for ABZSO and ABZSO2 were significantly higher (P &lt; 0.01) in the pigs fed on pasture, and were correlated with significantly longer elimination half-lives and mean residence times for both metabolites.
1. The effect of co-administration of either short- or long-acting formulations of DXM on hepatic... more 1. The effect of co-administration of either short- or long-acting formulations of DXM on hepatic function and the plasma pharmacokinetic behaviour of prochiral fenbendazole (FBZ) and its metabolites was evaluated in sheep. 2. Neither DXM treatment markedly affected any of the biochemical markers of hepatic function tested. In contrast, both formulations significantly modified the plasma pharmacokinetic behaviour of FBZ and its metabolites. 3. Plasma FBZ concentrations and the associated area under the time-concentration curves were significantly lower, although the plasma detection period was longer (72 versus 48 h) in the DXM pretreated animals compared with those given FBZ alone. 4. DXM also appeared to alter the pattern of FBZ absorption, possibly through effects on abomasal pH. The shape of the plasma concentration-time curves for oxfendazole (OFZ) and fenbendazole sulphone (FBZSO(2)) were similar to FBZ, raising the possibility that DXM treatment may have altered the liver biotransformation of the parent drug. 5. The concentrations of the (+) chiral metabolite of OFZ were significantly lower in DXM pretreated animals compared with those given FBZ alone. The trend was similar for the (-) antipode, although the differences between DXM pretreated and non-pretreated animals were not statistically significant.
Slight differences in formulation may change the plasma kinetics and ecto-endoparasiticide activi... more Slight differences in formulation may change the plasma kinetics and ecto-endoparasiticide activity of endectocide compounds. This work reports on the disposition kinetics and plasma availability of ivermectin (IVM) after subcutaneous (SC) and intramuscular (IM) administration as an oil-based formulation to cattle. Parasite-free Aberdeen Angus calves (n = 24; 240-280 kg) were divided into three groups (n = 8) and treated (200 microg/kg) with either an IVM oil-based pharmaceutical preparation (IVM-TEST formulation) (Bayer Argentina S.A.) given by subcutaneous (Group A) and intramuscular (Group B) injections or the IVM-CONTROL (non-aqueous formulation) (Ivomec, MSD Agvet) subcutaneously administered (Group C). Blood samples were taken over 35 days post-treatment and the recovered plasma was extracted and analyzed by HPLC using fluorescence detection. IVM was detected in plasma between 12 h and 35 days post-administration of IVM-TEST (SC and IM injections) and IVM-CONTROL formulations. Prolonged IVM absorption half-life (p &lt; 0.05) and delayed peak plasma concentration (p &lt; 0.001) were obtained following the SC administration of the IVM-TEST compared to the IVM-CONTROL formulation. No differences in total plasma availability were observed among treatments. However, the plasma residence time and elimination half-life of IVM were significantly longer after injection of the IVM-TEST formulation. IVM plasma concentrations were above 0.5 ng/ml for 20.6 (CONTROL) and 27.5 days (IVM-TEST SC), respectively (p &lt; 0.05). The modified kinetic behaviour of IVM obtained after the administration of the novel oil-based formulation examined in this trial, compared to the standard preparation, may positively impact on its strategic use in cattle.
Introduction: Enterococcus faecalis is a frequent etiologic agent of invasive infections in hospi... more Introduction: Enterococcus faecalis is a frequent etiologic agent of invasive infections in hospitalized patients. The aim of this study was to analyze clinical and microbiological features of bacteremia caused by E. faecalis. Methodology: Between 2011 and 2013, significant bacteremia caused by E. faecalis in hospitalized patients was studied. Patient characteristics, comorbid conditions, and 14-day mortality were recorded. Virulence genes esp, gelE, and cylA; opsonophagocytosis resistance; resistance to bactericidal effect of normal serum; beta lactamase production; and susceptibility to ampicillin, vancomycin, teicoplanin, gentamicin, and streptomycin were investigated. Results: E. faecalis strains were recovered from 33 bacteremic patients. Polymicrobial bacteremia was diagnosed in 2 patients; 10 patients died. Virulence genes were found in strains from both deceased patients and survivors. Sources of bacteremia included urinary tract infections (36.4%), vascular catheters (15.1%), abscesses (9.1%), and unknown (48.5%). Underlying diseases included cancer (30.3%), diabetes (36.4%), cirrhosis (6.1%), renal (36.4%), and chronic obstructive pulmonary disease (2.0%). Co-morbidities included alcohol use (26.1%); glucocorticoid therapy (19.0%); prior antibiotic therapy (60.6%); and central venous (21.2%), arterial (12.1%), and urinary (63.6%) catheters. Also, 57.6% of patients came from the intensive care unit (ICU); 33.3% had mechanical ventilation. Significant mortality-associated conditions included polymicrobial bacteremia, oncological disease, APACHE II score ≥ 20, ICU stay, renal disease, central venous catheter, and mechanical ventilation. Conclusions: Outcome of patients was associated with their status and not with the presence of virulence genes in E. faecalis strains. A significant percentage of bacteremia had undetermined origin. An alternate origin may be the gastrointestinal tract, through translocation.
Resistant Gram-positive bacteria are causing increasing concern in clinical practice. This work i... more Resistant Gram-positive bacteria are causing increasing concern in clinical practice. This work investigated the efficacy of AP-CECT7121 (an antimicrobial peptide isolated from an environmental strain of Enterococcus faecalis CECT7121) against various pathogenic Gram-positive bacteria. Strains were isolated from intensive care unit patients unresponsive to standard antibiotic treatments. Inhibitory activity of AP-CECT7121 was assessed using the agar-well diffusion method. The most resistant isolates from each species screened (Enterococcus faecium, Enterococcus faecalis,Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Clostridium perfringens and Clostridium difficile) were further examined in time-killing curve studies. These bactericidal kinetic experiments demonstrated a rapid killing effect with no viable bacteria being detected within 30 and 90 min for enterococcal and streptococcal strains and 180 min for community-acquired methicillin-resistant S. aureus and C. perfringens: viable counts for C. difficile were threefold decreased after 90 min. AP-CECT7121 may provide a novel strategy for treating potentially fatal clinical infections in hospitalized patients.
Argentina Biomedical Science has been historically strong. The development of Human and Veterinar... more Argentina Biomedical Science has been historically strong. The development of Human and Veterinary Pharmacology in our country as a pivotal discipline has been acknowledged worldwide because of the quality of its contributions. Argentinean Society of Experimental Pharmacology (SAFE) is a non- profit association whose research fields include Experimental and Clinical Pharmacology. SAFE main goals are described as follow: a) To meet active researchers for studying concerns regarding Experimental and Clinical Pharmacology, b) To launch an initiative for development of the discipline in mainly our country and other collaborative countries worldwide, c) To spread the pharmacological know-how obtained from different research teams, d) To strengthen relations between pharmacologists, e) To facilitate the presentation and discussion of scientific papers. This current article shows the SAFÉs more important scientific contribution to pharmacology through its former research scientists to the present.
The Journal of Infection in Developing Countries, 2015
Enterococcus faecalis is a frequent etiologic agent of invasive infections in hospitalized patien... more Enterococcus faecalis is a frequent etiologic agent of invasive infections in hospitalized patients. The aim of this study was to analyze clinical and microbiological features of bacteremia caused by E. faecalis. Between 2011 and 2013, significant bacteremia caused by E. faecalis in hospitalized patients was studied. Patient characteristics, comorbid conditions, and 14-day mortality were recorded. Virulence genes esp, gelE, and cylA; opsonophagocytosis resistance; resistance to bactericidal effect of normal serum; beta lactamase production; and susceptibility to ampicillin, vancomycin, teicoplanin, gentamicin, and streptomycin were investigated. E. faecalis strains were recovered from 33 bacteremic patients. Polymicrobial bacteremia was diagnosed in 2 patients; 10 patients died. Virulence genes were found in strains from both deceased patients and survivors. Sources of bacteremia included urinary tract infections (36.4%), vascular catheters (15.1%), abscesses (9.1%), and unknown (48.5%). Underlying diseases included cancer (30.3%), diabetes (36.4%), cirrhosis (6.1%), renal (36.4%), and chronic obstructive pulmonary disease (2.0%). Co-morbidities included alcohol use (26.1%); glucocorticoid therapy (19.0%); prior antibiotic therapy (60.6%); and central venous (21.2%), arterial (12.1%), and urinary (63.6%) catheters. Also, 57.6% of patients came from the intensive care unit (ICU); 33.3% had mechanical ventilation. Significant mortality-associated conditions included polymicrobial bacteremia, oncological disease, APACHE II score ≤ 20, ICU stay, renal disease, central venous catheter, and mechanical ventilation. Outcome of patients was associated with their status and not with the presence of virulence genes in E. faecalis strains. A significant percentage of bacteremia had undetermined origin. An alternate origin may be the gastrointestinal tract, through translocation.
Therapeutic failures attributed to medical management of cystic echinococcosis (CE) with albendaz... more Therapeutic failures attributed to medical management of cystic echinococcosis (CE) with albendazole (ABZ) have been primarily linked to the poor drug absorption rate resulting in low drug level in plasma and hydatid cysts. Lipid nanocapsules (LNCs) represent nanocarriers designed to encapsulate lipophilic drugs, such as ABZ. The goals of the current work were: (i) to characterize the plasma and cyst drug exposure after the administration of ABZ as ABZ-LNCs or ABZ suspension (ABZ-SUSP) in mice infected with Echinococcus granulosus, and ii) to compare the clinical efficacies of both ABZ formulations. Enhanced ABZ sulphoxide (ABZ-SO) concentration profiles were obtained in plasma and cysts from ABZ-LNC treated animals. ABZSO exposure (AUC0-LOQ) was significantly higher in plasma and cyst after the ABZ-LNC treatments, both orally and subcutaneously, compared to that observed after oral administration of ABZ-SUSP. Additionally, ABZSO concentrations measured in cysts from ABZ-LNC treated mice were 1.7-fold higher than those detected in plasma. This enhanced drug availability correlated with an increased efficacy against secondary CE in mice observed for the ABZ-LNCs, while ABZ-SUSP did not reach differences with the untreated control group. This new pharmacotechnically-based strategy could be a potential alternative to improve the treatment of human CE.
The current chemotherapy of cystic echinococcosis (CE) is mainly based on the use of albendazole,... more The current chemotherapy of cystic echinococcosis (CE) is mainly based on the use of albendazole, and the results have been shown to be highly variable. Thus, new and more efficient treatment options are urgently needed. The goals of the current study were: (a) to compare the ex vivo activity of flubendazole (FLBZ) and nitazoxanide (NTZ), given either separately or co-administered, against Echinococcus granulosus protoscoleces and cysts, (b) to characterize the plasma disposition kinetics of FLBZ administered alone or combined with NTZ in mice; (c) to compare the in vivo activity of FLBZ and NTZ (either each alone or as a combined treatment) against secondary CE developed in mice. Ex vivo drug activity study: E. granulosus protoscoleces and cysts were incubated either with FLBZ, NTZ, or the FLBZ-NTZ combination. Protoscoleces and cyst viability was monitored by the methylene blue exclusion test and scanning electron microscopy (SEM). Pharmacokinetic study: Balb/C mice received FLBZ (5mg/kg) orally either alone or co-administered with NTZ (100mg/kg). Blood samples were collected up to 12h post treatment and plasma analyzed for FLBZ/metabolites by HPLC. Clinical Efficacy study: following secondary infection, meaning i.p. injection of 1500 E. granulosus protoscoleces/animal (n=40), the both drugs were administered by intragastric inoculation on a daily basis for a period of 25 days. Balb/C mice received FLBZ (5mg/kg, twice a day) alone, NTZ (100mg/kg, once daily) alone or a combination of both molecules (FLBZ, 5mg/kg twice a day and NTZ, 100mg/kg, once daily). Ten untreated animals were used as a control. All animals were killed and the weight of the cysts collected from each animal was recorded. The presence of NTZ did not markedly affect the FLBZ kinetic parameters in mice. FLBZ alone or combined with NTZ induced a reduction (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) of cyst weight in comparison to the untreated control and NTZ-treated treated mice. The data obtained here indicate that NTZ did not affect hydatid cyst development in mice. Conversely, FLBZ shows an excellent efficacy against CE.
The pharmacokinetics of tylosin were compared in cattle (Bos taurus) and buffaloes (Bubalus bubal... more The pharmacokinetics of tylosin were compared in cattle (Bos taurus) and buffaloes (Bubalus bubalis). Six animals received each a single dose of 10 mg/kg of tylosin tartrate by the intramuscular route. The serum concentration (Cmax) and the volume of distribution (Vd) presented significant differences between the two species. Cmax was 0.40 +/- 0.046 microg/ml for buffaloes and 0.64 +/- 0.068 microg/ml for cattle. Vd was 1.91 +/- 0.12 L/kg and 1.33 +/- 0.09 L/kg for buffaloes and cattle, respectively. However, as the present study did not show considerable differences in the pharmacokinetics of tylosin in buffaloes and cattle, similar dosage regimes of this drug can be recommended for both species.
The current experiments compare the pattern of ex vivo uptake (diffusion) of albendazole (ABZ) an... more The current experiments compare the pattern of ex vivo uptake (diffusion) of albendazole (ABZ) and albendazole sulfoxide (ABZSO) by Ascaris suum and Fasciola hepatica. Specimens of A. suum and F. hepatica were collected from untreated animals (pigs and sheep, respectively) and incubated with either ABZ or ABZSO for different time periods (5-180 min). After incubation. the parasite material was analysed by HPLC to quantify the amount of ABZ and/or ABZSO. The parent drug and its active ABZSO metabolite were recovered from the parasites after ex vivo incubation for different time periods throughout the assay. Total drug availability in A. suum, expressed as area under the concentration versus time curve (AUC) over 180 min of incubation, was significantly greater (P<0.05) for ABZ parent drug (AUC = 4.19 +/- 0.59 microg x h xg(-1)) compared with the more polar ABZSO metabolite (AUC = 0.25 +/- 0.01 micro x h x g(-1)). Similar results were observed after the incubation of both molecules...
We evaluated the comparative plasma and abomasal fluid disposition kinetics of albendazole (ABZ) ... more We evaluated the comparative plasma and abomasal fluid disposition kinetics of albendazole (ABZ) and its metabolites in calves either grazing on pasture or fed a grain-based concentrate diet. Six male Holstein calves (weight 180 to 200 kg) were allowed to graze on lush pasture for three weeks before intraruminal administration of ABZ at 10 mg kg-1(pasture group). After a three-week wash-out period, the same animals were housed and fed on a grain-based concentrate diet for three weeks prior to receiving the same ABZ treatment (concentrate group). Jugular blood and abomasal fluid samples were collected over 120 hours post-treatment. Plasma and abomasal fluid samples were analysed by high performance liquid chromatography (HPLC). The digesta transit time was measured using cobalt (Co) as a fluid marker; abomasal fluid and faecal samples were collected and Co concentrations measured by atomic absorption spectrophotometry. Complementary studies of the in vitro dissolution of ABZ particle...
The influence of diet on the disposition kinetics of albendazole (ABZ) and its metabolites in pig... more The influence of diet on the disposition kinetics of albendazole (ABZ) and its metabolites in pigs was investigated. ABZ was administered orally at 10 mg kg-1 to pigs fed either a commercially produced 35 per cent protein/grain concentrate diet (concentrate group), a whey-based diet supplemented with corn grain (whey/grain group) or grazed on pasture (pasture group). Blood samples were taken serially for 96 hours and plasma was analysed by high performance liquid chromatography (HPLC) for ABZ, ABZ sulphoxide (ABZSO), ABZ sulphone (ABZSO2) and amino-ABZSO2 (NH2ABZSO2). ABZ was not detected in plasma at any time after the treatment, and ABZSO and ABZSO2 were the main metabolites detected between 0.5 and 30 to 48 hours after treatment in all the experimental animals. Low concentrations of the NH2ABZSO2 metabolite were found in plasma between 18 and 36 hours after the administration of ABZ to all the groups of pigs. The pharmacokinetic behaviour of the ABZ metabolites in pigs fed either the concentrate of the whey/concentrate diet was substantially different from that observed in pigs grazing on pasture. The peak concentration (C(max)) and areas under the concentration-time curves (AUC) for ABZSO and ABZSO2 were significantly higher (P &lt; 0.01) in the pigs fed on pasture, and were correlated with significantly longer elimination half-lives and mean residence times for both metabolites.
1. The effect of co-administration of either short- or long-acting formulations of DXM on hepatic... more 1. The effect of co-administration of either short- or long-acting formulations of DXM on hepatic function and the plasma pharmacokinetic behaviour of prochiral fenbendazole (FBZ) and its metabolites was evaluated in sheep. 2. Neither DXM treatment markedly affected any of the biochemical markers of hepatic function tested. In contrast, both formulations significantly modified the plasma pharmacokinetic behaviour of FBZ and its metabolites. 3. Plasma FBZ concentrations and the associated area under the time-concentration curves were significantly lower, although the plasma detection period was longer (72 versus 48 h) in the DXM pretreated animals compared with those given FBZ alone. 4. DXM also appeared to alter the pattern of FBZ absorption, possibly through effects on abomasal pH. The shape of the plasma concentration-time curves for oxfendazole (OFZ) and fenbendazole sulphone (FBZSO(2)) were similar to FBZ, raising the possibility that DXM treatment may have altered the liver biotransformation of the parent drug. 5. The concentrations of the (+) chiral metabolite of OFZ were significantly lower in DXM pretreated animals compared with those given FBZ alone. The trend was similar for the (-) antipode, although the differences between DXM pretreated and non-pretreated animals were not statistically significant.
Slight differences in formulation may change the plasma kinetics and ecto-endoparasiticide activi... more Slight differences in formulation may change the plasma kinetics and ecto-endoparasiticide activity of endectocide compounds. This work reports on the disposition kinetics and plasma availability of ivermectin (IVM) after subcutaneous (SC) and intramuscular (IM) administration as an oil-based formulation to cattle. Parasite-free Aberdeen Angus calves (n = 24; 240-280 kg) were divided into three groups (n = 8) and treated (200 microg/kg) with either an IVM oil-based pharmaceutical preparation (IVM-TEST formulation) (Bayer Argentina S.A.) given by subcutaneous (Group A) and intramuscular (Group B) injections or the IVM-CONTROL (non-aqueous formulation) (Ivomec, MSD Agvet) subcutaneously administered (Group C). Blood samples were taken over 35 days post-treatment and the recovered plasma was extracted and analyzed by HPLC using fluorescence detection. IVM was detected in plasma between 12 h and 35 days post-administration of IVM-TEST (SC and IM injections) and IVM-CONTROL formulations. Prolonged IVM absorption half-life (p &lt; 0.05) and delayed peak plasma concentration (p &lt; 0.001) were obtained following the SC administration of the IVM-TEST compared to the IVM-CONTROL formulation. No differences in total plasma availability were observed among treatments. However, the plasma residence time and elimination half-life of IVM were significantly longer after injection of the IVM-TEST formulation. IVM plasma concentrations were above 0.5 ng/ml for 20.6 (CONTROL) and 27.5 days (IVM-TEST SC), respectively (p &lt; 0.05). The modified kinetic behaviour of IVM obtained after the administration of the novel oil-based formulation examined in this trial, compared to the standard preparation, may positively impact on its strategic use in cattle.
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Papers by Sergio Bruni