Papers by Lubomir D Lashev
Investigations into some haematological values in birds from three Columbidae species e.g. pigeon... more Investigations into some haematological values in birds from three Columbidae species e.g. pigeons, (Columba livia domestica), collared doves (Streptopelia decaocto) and African collared doves, (Streptopelia roseogrisea) have been performed. In all three species, high haemoglobin concentrations, and respectively high red blood cell counts were observed. In S. decaocto the red blood cell count was extremely high, corresponding to the high haemoglobin levels. RBC values in both Streptopelia species were signifi cantly higher than in domestic pigeons. Higher white blood cell counts were present in freely living collared doves versus both species living in captivity. The heterophils/lymphocytes ratio in African collared doves was the highest − 1.05, followed by the ratios of collared doves and domestic pigeons.
Veterinarski Arhiv, 2017
The pharmacokinetics of enrofloxacin (EFC) was investigated in ducks fed with a normal diet, and ... more The pharmacokinetics of enrofloxacin (EFC) was investigated in ducks fed with a normal diet, and in force-fed ducks, after a single intravenous (i.v.) and oral (p.o.) administration at doses of 10 mg/kg. Serum concentrations of EFC and ciprofloxacin (as metabolite of EFC) were determined by the HPLC method. The elimination half-lives of EFC after i.v. administration and compartmental pharmacokinetic analysis were 4.62 ± 0.62h and 6.39 ± 2.78 h in healthy and force-fed ducks, respectively. The values of total body clearance were 0.24 ± 0.03 L/h/kg in healthy and 0.18 ± 0.02 L/h/kg in force-fed ducks. The values of the volume of distribution (V ss) were 1.32 ± 0.18 L/kg and 1.31 ± 0.21 L/kg, respectively. After oral administration, maximum serum concentrations were 1.95 ± 0.36 µg/mL reached at 3.67 ± 4.26 h, and 4.25 ± 1.21 µg/mL at 1.25 ± 0.88 h, respectively. The serum concentrations of ciprofloxacin were significantly lower in the force-fed ducks. Longer enrofloxacin residence in force-fed ducks can be expected if compared to normally fed animals.
The control of coccidiosis in chickens is undertaken mainly by administration of anticoccidial dr... more The control of coccidiosis in chickens is undertaken mainly by administration of anticoccidial drugs. Sulfachloropyrazine-sodium is still used as an effective coccidiocidal compound to treat poultry with clinical signs of coccidiosis. However, its disposition after three days treatment in Eimeria tenella infected chickens has not been well studied. Pharmacokinetics of sulfachlorpyrazine-sodium was investigated in healthy chickens and chickens experimentally infected with E. tenella. Serum and tissue concentrations were determined by HPLC-PDA analysis. The values of absorption half-life (17.24 ± 3.50 h) and time for achievement of maximal serum concentrations Tmax (23.41 ± 3.78 h) of the sulfonamide were significantly higher in infected chickens. An accumulation index of 1.22 ± 0.13 was estimated and significantly higher serum concentrations were observed in E. tenella challenged animals. Significantly higher sulfachloropyrazine-sodium levels were found in the duodenum, caeca and the...
Abstract: Allometric analysis of the total body clearance (Cl B), steady-state volume of distribu... more Abstract: Allometric analysis of the total body clearance (Cl B), steady-state volume of distribution (V ss) and elimination half-life (t 1/2) based on the literature data in fish species was performed for oxolinic acid, flumequine, enrofloxacin. Values of Cl B and V ss show allometric dependence on body weight but values of t 1/2 can not be predicted after scaling toward body weight. Significant differences were found between allometric equations characteristic for the fish species and the homeotherm species. These results are reflectors of the differences in the level of the metabolic rate between cold-blooded and warm-blooded animal species.
Turkish Journal of Veterinary & Animal Sciences, 2009
The pharmacokinetics of gentamicin, tobramycin, amikacin, kanamycin, and apramycin were investiga... more The pharmacokinetics of gentamicin, tobramycin, amikacin, kanamycin, and apramycin were investigated after single intravenous administration in goats. Their antimicrobial activity against 30 strains of Staphylococcus aureus isolates from goats was also studied. On the base of the pharmacokinetic and pharmacodynamic data, a comparison between antibiotics was made. All 5 antibiotics showed a marked high in vitro antibacterial activity. The lowest MIC90 values were those of amikacin and the highest one was of kanamycin. The ratios of Cmax/MIC showed that amikacin has an advantage of providing the highest values of the concentration/MIC 90 ratio, as well of the time providing bactericidal levels, followed by apramycin, whereas the other 3 antibiotics had comparable values, but lower than the first 2 antibiotics. The same interpretation could be made for the area under the curve/MIC 90 ratio.
Veterinarski Arhiv, 2009
1Department of Pharmacology, Veterinary Physiology and Physiological Chemistry, Faculty of Veteri... more 1Department of Pharmacology, Veterinary Physiology and Physiological Chemistry, Faculty of Veterinary Medicine, Trakia University, Bulgaria 2Department of Surgery, Faculty of Veterinary Medicine, Trakia University, Bulgaria 3Department of Internal Diseases, Faculty of Veterinary Medicine, Trakia University, Bulgaria 4High School of Veterinary Medicine, Stara Zagora, Bulgaria 5Department of Morphology, Animal Physiology and Nutrition, Faculty of Agriculture, Trakia University, Bulgaria
Bulgarian Journal of Veterinary Medicine, 2008
Summary Lashev, L. & D. J. Dimitrova, 2008. Comparative allometric analysis of three isoxazolylpe... more Summary Lashev, L. & D. J. Dimitrova, 2008. Comparative allometric analysis of three isoxazolylpenicillins in four mammalian species. Bulg. J. Vet. Med. , 11, No 4, 269 273. Comparative allometric analysis of selected pharmacokinetic parameters of cloxacillin, dicloxacillin and flucloxacillin in four animal species (cats, dogs, pigs and sheep) was performed. The correlations between the total body clearance (CL B) and the volume of distribution (Vd area ) to the body weight of animals were established. They can be expressed by the equations: cloxacillin CL B =5.68W 1.18 , Vd area =0.24W 1.56 ; dicloxacillin CL B=17.95W 0.92 , Vd area =2.93W 0.62 ; and flucloxacillin CL B=10.59W 0.97 , Vd area =1.52W 1.43 . No statistically significant correlation was found for the half-life values.
The pharmacokinetics of tobramycin was investigated in 6 weeks old broiler chickens after three w... more The pharmacokinetics of tobramycin was investigated in 6 weeks old broiler chickens after three ways of administration (i.v., i.m. and p.o. at doses of 5 mg/kg, for each route and 20 mg/kg orally). Microbiological method was used for the antibiotic determination and non-compartment analysis for pharmacokinetic calculations. It was observed that tobramycin was absorbed very well after i.m. and poorly after oral administration. Its distribution was relatively high compared to other aminoglycosides and other species and was eliminated quickly.
Bulgarian Journal of Veterinary Medicine, 2017
Allometric analysis of the total body clearance (Cl B), steady-state volume of distribution (V ss... more Allometric analysis of the total body clearance (Cl B), steady-state volume of distribution (V ss) and elimination half-life (t 1/2) was performed for cephalexin, cefepime, cefquinone and ceftriaxone based on literature data in mammalian species. Values of Cl B and V ss show allometric dependence on body weight, while values of t 1/2 could not be predicted correctly after scaling toward body weight. The equations based on the calculations which could be used for estimation of the respective pharmacokinetic parameters are as follows: Cephalexin: Cl B =0.20W 1.05 ; Vss=0.32W 0.98 ; Cefepime: t 1/2β =1.03W 0.16 ; Cl B =0.35W 0.68 ; V ss =0.133W 0.99 ; Ceftriaxone: t 1/2β =0.83W 0.13 ; Cl B =0.76W 0.73 ; V ss =0.82W 0.79 ; Cefquinome: Cl B =0.22W 0.875 ; V ss =0.298W 0.975 .
Macedonian Veterinary Review, 2016
The pharmacokinetics of doxycycline was investigated in force-fed and normally fed ducks after si... more The pharmacokinetics of doxycycline was investigated in force-fed and normally fed ducks after single intravenous (i.v.) and oral (p.o.) administration at a dose of 15 mg/kg bw. Serum concentrations of the drug were determined by the HPLC method. Pharmacokinetic parameters were calculated using compartmental analysis. Serum concentrations of doxycycline after i.v. administration in both groups were not statistically different. The values of half-lives were 5.82±1.85 h and 6.06±5.51 h in normal and force-fed birds. The total body clearance was respectively 0.40±0.05 L/h/kg and 0.34±0.10 L/h/kg, and volume of distribution (V
Veterinary Research Communications, Nov 1, 2006
Colibacillosis is a systemic disease responsible for important economic losses in poultry breedin... more Colibacillosis is a systemic disease responsible for important economic losses in poultry breeding; fluoroquinolones, including danofloxacin, are used to treat diseased animals. The purpose of the present study was to estimate pharmacokinetic-pharmacodynamic (PK-PD) surrogates for bacteriostasis, bactericidal activity and bacterial elimination against Escherichia coli O78/K80, using a PK-PD approach, for danofloxacin in turkeys after oral administration. Eight healthy turkeys, breed BUT 9, were included in a two-way crossover study. The drug was administered intravenously (i.v.) and orally at a dose rate of 6 mg/kg bw. The values of the elimination half-life and the total body clearance after i.v. administration were 8.64 ± 2.35 h and 586.76 ± 136.67 ml kg -1 h -1 , respectively. After oral administration, the values of the absolute bioavailability and the elimination half-life were 78.37 ± 17.35% and 9.74 ± 2.93 h, respectively. The minimum inhibitory concentration against the investigated strain in turkey serum was 0.25 μg/ml, four times higher than in broth. The lowest effective ex vivo AUC 24 /MIC ratios required for bacteriostasis, bactericidal activity, and total killing of E. coli O78/K80 were 0.416 h, 1.9 h and 6.73 h, respectively. The oral dose of 6 mg/kg used in the present study could be interpreted as being sufficient to eliminate E. coli with an MIC 0.25 μg/ml. However, considering the demand that antimicrobial resistance should be avoided by complete bacterial elimination, PK-PD considerations suggest that an even higher dose of 32 mg/kg per day or 0.7 mg/kcal per day should be evaluated in clinical trials.
Turkish Journal of Veterinary and Animal Sciences, 2007
The aim of the present study was to determine the changes in some blood biochemical and haematolo... more The aim of the present study was to determine the changes in some blood biochemical and haematological parameters in healthy female goats after a 5-day parenteral treatment with gentamicin (4 mg/kg), tobramycin (5 mg/kg), amikacin (10 mg/kg), kanamycin (10 mg/kg), apramycin (20 mg/kg), and spectinomycin (20 mg/kg). The results indicated that aminoglycosides caused more severe alterations than aminocyclitols, especially on those parameters related to renal function. There was a tendency toward a rise in plasma creatinine and urea levels after aminoglycoside treatment, as well as a rise in urea levels after aminocyclitol administration. These antibiotics caused decreases in plasma or serum glucose, sodium and chloride levels, erythrocytes and leukocytes counts, haematocrit percentage and haemoglobin concentration. For plasma or serum total protein, total lipids, lactate dehydrogenase, alkaline phosphatase, calcium, and magnesium concentrations and differential white blood cell counts, various changes occurred. As a whole, these antibiotics have the potential to alter biochemical and haematological values in female goats after their use at therapeutic doses.
BULGARIAN JOURNAL OF VETERINARY MEDICINE, 2015
An analysis of literature data about routine haematological parameters of avian species from the ... more An analysis of literature data about routine haematological parameters of avian species from the Galliformes order is made. Data for the following gallinaceous birds were included: wild and domesticated chicken breeds, common pheasant, quail, turkey, peafowl and guinea fowl. Data for red and white blood picture indices such as haemoglobin, red blood cells (RBC), packed cell volume (PCV), total and differential white blood cell (WBC) counts from the literature as well as own data were used. Gender-related differences were reported by most of authors for RBC, haemoglobin and PCV with higher values in male birds from the Gallus gallus species. Similar results were not found in other species of the order. In most of the cases no statistically significant interspecies or gender-related differences in WBC counts were registered. Tendencies for higher heterophil/lymphocyte ratios (H/L) in male birds were also registered. Differences related to the breed, result of various degree of domestication, were not identified.
Journal of Veterinary Pharmacology and Therapeutics, 2008
MDR1, MRP2 and BCRP are members of the superfamily of ABC membrane transporters that export a lar... more MDR1, MRP2 and BCRP are members of the superfamily of ABC membrane transporters that export a large variety of structurally diverse substances out of the cell, hence being an integral part of various biological barriers. Here we report for the first time the tissue distribution of these ABC efflux transporters in the gastrointestinal tract (crop, proventriculus, duodenum, proximal and distal jejunum, ileum, caecum, colon) as well as in liver, kidney, lung, brain, adrenal gland, ovaries, oviduct and testes in BUT9 turkeys. MDR1 and BCRP mRNA expression was detected in all tissue samples, and the highest levels were measured in the small intestines. The tissue distribution of MRP2 mRNA was less consistent and some tissues seemed to lack any significant expression. Moreover, in consideration of previous findings suggesting that fluoroquinolones are substrates and modulators of ABC transporters, the effect of orally administered danofloxacin mesylate on the levels of MDR1, MRP2 and BCRP mRNA expression was investigated. Danofloxacin treatment resulted in a significant up-regulation of the measured transporters at the transcriptional level in the upper part of gastro-intestinal tract, liver and kidneys as well as in barrier-protected organs, such as the brain. However, despite this significant increase in the transcription levels, the pharmacokinetic parameters after repeated application of danofloxacin mesylate were not significantly altered.
Antimicrobial Agents and Chemotherapy, 2006
Fluoroquinolones are extensively used in the treatment of systemic bacterial infections in poultr... more Fluoroquinolones are extensively used in the treatment of systemic bacterial infections in poultry, including systemic Escherichia coli bacillosis, which is a common disease in turkey flocks. Marbofloxacin has been licensed for use in various mammalian species, but not as yet for turkeys, although its kinetic properties distinguish it from other fluoroquinolones. For example, the longer half-life of marbofloxacin in many animal species has been appreciated in veterinary practice. It is generally accepted that, for fluoroquinolones, the optimal dose should be estimated on the basis of the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the drug under consideration. Knowledge of these specific data for the target animal species allows the establishment of an integrated PK-PD model that is of high predictive value. In the present study, the antibacterial efficacy (PD indices) against a field isolate of Escherichia coli O78/K80 was investigated ex vivo following oral an...
Bulgarian Journal of Veterinary Medicine, 2012
The purpose of this study was to examine the allometric relationships of fluoroquinolones, penici... more The purpose of this study was to examine the allometric relationships of fluoroquinolones, penicillins, aminoglycosides, sulfonamides, tetracyclines and florfenicol in bird species using pharmacokinetic data from the literature. The parameters of interest (half-life, volume of distribution, and total body clearance) were correlated as a function of body weight applying an allometric approach (Y=aW b ). Values of the coeficient a and the exponent b were close to the theorethical values for the clearance and volume of distribution of most drugs, except for sulfadimidine, tobramycin and apramycin. The elimination half-life was relatively independent of body mass for penicillins, pefloxacin, doxycycline and trimethoprim. Results of the analysis suggest that allometric scaling can be used as a tool for predicting pharmacokinetic parameters for most drugs in avian species. The predictive power is stronger, when only data for bird species are included, in comparison to simultaneous allometric scaling of the data for avian and mammalian species.
ФАРМАКОКИНЕТИКА НА ЕНРОФЛОКСАЦИН ПРИ ПАТИЦИ СЪС СТЕАТОЗА СЛЕД УГОЯВАНЕ
Енрофлоксацин (EFC) е флуоориран хинолон от втора генерация с широк антимикробен спектър, който е... more Енрофлоксацин (EFC) е флуоориран хинолон от втора генерация с широк антимикробен спектър, който е разработен за приложение изключително за ветеринарната медицина. Активен е срещу много Грам-положителни и Грам-отрицателни микроорганизми. Фармакокинетиката му е изучавана при много видове птици, като са установени ясни междувидови различия в поведението му. В животинският организъм EFC частично се трансформира до ципрофлоксацин – субстанция имаща също антимикробна активност. Въпреки мнения, че когато угояването на патици се извършва в съответствие с професионалните стандарти, то не индуцира патологични промени свързани с храненето и стеатозата е обратима, по време на този период се наблюдават промени във физиологията на птиците, като увеличено телесно тегло, триглицеридемия, високи стойности на АЛАТ и липаза в кръвта. Такъв тип промени могат да доведат до изменения в резорбцията, разпределението и елиминацията на лекарствени вещества, прилагани в случай на заболяване и необходимост от ...
Comparison of plasma and tissue disposition of enrofloxacin in rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio) after a single oral administration
Http Dx Doi Org 10 1080 19440049 2014 983998, Dec 23, 2014
The aim of the study was to investigate the serum and tissue disposition of enrofloxacin and its ... more The aim of the study was to investigate the serum and tissue disposition of enrofloxacin and its active metabolite ciprofloxacin in rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio) after a single oral administration at a dose of 10 mg kg(-1). Concentrations of enrofloxacin in the serum of rainbow trout showed high variability with two peaks at the third and 24th hour after administration. The highest concentrations were found in the liver. The curves of liver levels showed similar changes to the respective serum samples. In the muscles, enrofloxacin concentrations were also higher compared with the respective serum samples. Ciprofloxacin concentrations were lower and showed smaller variations in all investigated tissues. The serum and tissue concentrations of enrofloxacin and ciprofloxacin in common carp showed two peaks, with the first Cmax at the third hour after drug administration as in rainbow trout. Concentrations of both investigated substances were higher in the liver than in the serum. The differences in common carp were less pronounced in comparison with rainbow trout. Relatively high levels of both substances were found in the muscles. Seven days after treatment enrofloxacin concentrations in the serum and tissues were within the therapeutic levels for most of the sensitive microorganisms in trout. Lower concentrations of its metabolite ciprofloxacin were found in the investigated tissues at the last sampling point. Lower levels of both substances were found in carp.
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Papers by Lubomir D Lashev