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Comparative pharmacokinetics of ampicillin-sulbactam combination in calves and sheep
The pharmacokinetics of ampicillin and sulbactam administered in combination were studied in calves and sheep. The animals were administered an aqueous solution of ampicillin/sulbactam (2:1, w/w) intravenously and intramuscularly at doses of 13.2 and 6.6 mg.kg-1, respectively. A microbiological method was used to detect ampicillin, and HPLC was used to detect sulbactam in serum. Following intravenous (i.v.) administration, the distribution phases were rapid and similar (about 15 min) for both drugs in both species, whereas sulbactam in calves and ampicillin in sheep showed a faster elimination rate. After intramuscular (i.m.) administration both drugs showed peak concentrations higher in calves than in sheep; the peak time of sulbactam was shorter in calves than in sheep. No other significant differences in the pharmacokinetics of the combination were observed between the species after i.m. injection. The mean residence and absorption times, calculated by non-compartmental analysis, for both calves and sheep suggested that the differences in ampicillin and sulbactam pharmacokinetics could be attributable to the different molecular structures
Pharmacokinetic profile of sulphamonomethoxine-trimethoprim in horses after intravenous, intramuscular and oral administration
The pharmacokinetic profile of a sulphamonomethoxine-trimethoprim (SMM-TMP) combination was investigated in five horses. The combination was administered intravenously, intramuscularly and orally at a constant dose of 20 mg smm plus 4 Mg Tmp kg-1 bodyweight. Following intravenous administration both drugs dispersed rapidly with distribution half-lives of about 12 minutes for smm and about 18 minutes for TMP. Elimination half-lives for intravenous, intramuscular and oral administration were closely similar, indicating that elimination was independent of administration route. Bioavailability of the drugs in aqueous solution was good: about 72 per cent and 84 per cent for SMM and about 84 per cent and 98 per cent for TMP following intramuscular and oral administration, respectively. It is concluded that SMM-TMP administered orally once a day at 20 mg and 4 mg kg-1 bodyweight, respectively, maintains therapeutic concentrations, whereas twice daily intramuscular administration would be more effective for treating systemic infections in the horse than the once a day regimen usually adopted in veterinary practice
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Kinetic aspects of flumequine after repeated intramuscular administration in lactating cows
Flumequine (FLU) is a 2nd generation quinolone commonly used in food-producing species to control infection caused by various Gram-negative bacteria. Despite the availability of newer fluoroquinolones, FLU is still employed in several animal species mainly due to its relative low cost and good tolerability.
FLU was intramuscularly administered to healthy lactating cows, with a priming dose of 6 mg.kg-1 b.w. followed by 5 maintenance doses of 3 mg.kg-1 every 12 h. Blood samples were taken between 0.5 and 84 h, while milk samples were collected every 12 h during treatments and for the 10 milkings after. FLU serum and milk concentrations were determined by a validated HPLC method.
FLU reached mean peak serum concentration (Cmax 0.70±0.06 μg.ml-1) at about 4 hours (Tmax 3.32±0.65 h) and was still detected 84 h after treatments (mean 0.14±0.03 μg.ml-1). A mono-compartmental analysis was carried out on serum data (WinNonLin 5.0.1): after repeated administration mean AUC(0-∞) and t1/2el were 11.90±1.11 (hr*μg.ml-1) and 9.14±0.53 (h), respectively.
Milk concentration were above LOQ (25 μg.kg-1) only after priming dose (mean 40.42±13.69 μg.kg-1). During maintenance doses FLU decreased at values close to LOQ and rapidly disappeared after last treatment (60 h). The very low milk concentrations did not allow to perform kinetic analysis.
Serum concentrations after IM administrations can be considered efficacious against systemic infections during acute mastitis; nevertheless, FLU concentrations in milk seem too low to assure therapeutic effectiveness towards udder Gram-negative infections
Development and validation of an LC–MS/MS/MS method for the quantification of fluoroquinolones in several matrices from treated turkeys
The study presents a sensitive and reliable confirmatory method for the extraction, identification, quantification of five fluoroquinolones (FQ) namely enrofloxacin, ciprofloxacin, difloxacin, sarafloxacin and flumequine, in plasma, liver, kidney, muscle, skin + fat, lung and intestinal content from turkeys.
For the extraction and matrix clean-up of FQ residues from all biological matrices, the Quick Easy Cheap Effective Rugged Safe (QuEChERS) methodology was adopted; only for plasma samples acetonitrite was used.
The analyses were performed by liquid chromatography with mass spectrometry detection (LC-MS). LC separation was performed on a C18 Kinetex column (100 x 2.1 mm, 2.6 mu m, Phenomenex, CA, USA) with gradient elution using ammonium acetate solution (10 mM, pH 2.5) and methanol containing 0.1% formic acid. Mass spectrometric identification was done using an LTQ XL ion trap (Thermo Fisher Scientific, CA, USA), with a heated electrospray ionization probe, in positive ion mode.
The method was validated according to the European Legislation (decision 2002/657/EC) and EMA guideline (EMA/CVMP/VICH/463202/2009); selectivity, linearity response, trueness (in terms of recovery), precision (within-day repeatability and within-laboratory reproducibility), limit of detection, limit of quantification, decision limits, detection capability, absolute recovery and robustness were evaluated using turkey blank matrices. All data were within the required limits established for confirmatory methods except for flumequine which presented a recovery value slightly higher than 110% in muscle and intestinal content. For all FQs, all the extraction rates were greater than 70% and limits of quantification ranged from 1.2 mu g kg(-1) to 118.8 mu g kg(-1).
This fast and robust method was suitable for the identification and quantification of FQ residues in tissues, plasma and intestinal content as confirmed by data obtained from incurred samples of turkeys treated at farm for therapeutic purposes
Comparative production of the active metabolite o-desmethyl-tramadol (M1) in domestic animal species
Tramadol is an analgesic drug acting centrally and structurally related to morphine, which interacts with opioid receptors and inhibits the reuptake of noradrenaline and serotonine (1). In veterinary medicine tramadol has been recently authorised for the use in dog, and its efficacy for the management of moderate to severe postoperative pain has been assessed in dogs (2) and other domestic species where the extra label use of commercial preparations is adopted. In man and laboratory animal species, tramadol is metabolized in the liver; one of the main product, the O-desmethyl (M1) metabolite, with about 200 fold higher affinity for the opioid μ receptors than the parent compound is produced by the cytochrome P450 enzyme CYP2D6(3).
Aim of this work was the preliminary study of M1 production among cats, dogs and horses, as several indications suggest that it plays a significant role in the analgesic effect of tramadol also in this domestic animal species.
Tramadol was administered intravenously at the dose of 2 mg.kg-1 in dogs (n. 3) undergoing tibial plateau leveling osteotomy and cats (n. 8) subject to castration and at
2.5 mg.kg-1 in horses (n. 5) undergoing clinical examinations. Blood samples were collected before treatment, and at regular intervals from five minutes to eight hours after administration. Tramadol and its M1 metabolite, were assayed in serum by HPLC with fluorescence detection (4). To describe drugs kinetic behaviour, a bicompartmental analysis was used for tramadol, while for the M1 metabolite a non-compartmental analysis was performed.
The M1 metabolite attained concentrations much greater than 10 ng/ml, the lowest concentration associated with its therapeutic efficacy in humans (2), immediately after administration and were equal or above this threshold value for the whole period (8 h) in all the species studied. The behaviour of M1 in cats resulted different from what observed in horses and dogs. In cats the early appearance of M1 metabolite supported an intense metabolism of phase 1, while the relatively higher persistence of M1 could be related to the low activity of glucurono-coniugation typical of this species.
1) Grond S. & Sablotzki A. (2004) Clin Pharmacokin. 43: 879-923. 2) Kukanich B. & Papich M.G. (2004) J. vet. Pharmacol Ther. 27: 239-246. 3) Scott L.J.& Perry C.M., (2000) Drugs. 60: 139-176. 4) Bianchi M., Ferrario P., Panerai A.E. (2002), Analgesia; 6: 39-42.
Acknowledgment: The Authors kindly thank Formevet S.p.A.(Milano) for the support provided
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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