Improved culture of Histomonas meleagridis in a modification of Dwyer medium

Dwyer medium is the most frequently employed culture medium for Histomonas meleagridis. Both for subculturing and for resuscitation of H. meleagridis from storage in liquid nitrogen, modified Dwyer medium with an increased rice powder concentration (0.8%) and no chicken embryo extract proved superior to Dwyer standard medium, with threefold (10(6.3) vs. 10(5.8) histomonads/ml) to 10-fold (10(6.7) vs. 10(5.8) histomonads/ml) higher concentrations of parasites after resuscitation or subculturing, respectively.     

A virulent mono-eukaryotic culture of Histomonas meleagridis is capable of inducing fatal histomonosis in different aged turkeys of both sexes, regardless of the infective dose

Histomonosis (syn. histomoniasis) is a parasitic disease which affects predominately turkeys but also other avian species. Concurrent with the ban of therapeutic and prophylactic substances, the disease, caused by the flagellated protozoon Histomonas meleagridis, is more frequently reported. Due to somewhat diverse results reported in the past, a well-characterized culture was used in the present study to investigate the possible influence of certain parameters on the outcome of the disease. For this study, turkeys were infected with different doses of the mono-eukaryotic culture Histomonas meleagridis/Turkey/Austria/2922-C6/04 using birds of both sexes at various ages. All study groups consisted of 14 birds, of which 10 birds were directly infected via the cloacal route and four birds were kept as in-contact birds. This scheme was used to investigate the pathogenicity of the cloned isolate in 1-day-old and 14-day-old turkeys. In 8-week-old turkeys, only eight birds out of 12 were infected. When 1-day-old and 8-week-old turkeys were infected with 10(4) histomonads per bird, all turkeys died between 11 and 21 days postinfection or had to be euthanatized due to their poor condition. In a group of 14 poults, infective doses of either 10 histomonads (100 histomonads among 10 birds) or 10(3) histomonads per bird had hardly any influence on the first notification of clinical signs. However, even though the onset of clinical signs and mortality was delayed with the lower dose, none of the birds survived the infection. As a consequence, no differences were noticed between male and female turkeys using the mono-eukaryotic culture of Histomonas meleagrigis/Turkey/Austria/2922-C6/04 in the current experimental setting.     

Pharmacokinetics of ivermectin in llamas (Lama glama)

The pharmacokinetic behaviour of ivermectin was investigated in adult llamas (Lama glama) by using high performance liquid chromatography with a lower limit of quantification of 2 ng/ml to measure its concentration in serum. Llamas were treated with one of three commercial formulations (injectable, pour-on or oral paste) at dosages recommended by the manufacturer, or with an experimental injectable sustained-release formulation. In five llamas given 1 per cent ivermectin subcutaneously at 200 microg/kg, the median peak serum concentration (Cmax) was 3 ng/ml and the area under the serum concentration-time curve (AUC) was 13.5 ng x day/ml. In six llamas treated topically with 0.5 per cent ivermedin pour-on at 500 microg/kg, Cmax was 2.5 ng/ml or less and the AUC was 7.75 ng x day/ml or less. In seven llamas with measurable concentrations of ivermedin, the median times to peak serum concentration (tmax) were six days after subcutaneous injection and seven days after treatment with the pour-on formulation. In six llamas, the serum concentration of ivermectin remained less than 2 ng/ml for 124 hours after treatment with a 1.87 per cent oral paste at 200 microg/kg. In five llamas treated subcutaneously with 25 per cent ivermectin sustained-release microspheres at 1500 microg/kg, the median Cmax was 5 ng/ml and the median AUC was 224 ng x day/ml.     

Infection of turkeys with Histomonas meleagridis by the cloacal drop method

The infection of turkeys with Histomonas meleagridis was attempted in the absence of its normal vector Heterakis gallinarum, using several experimental techniques. Battery-reared poults were inoculated at 2 wk of age with histomonads cultured in vitro, by several routes, including (a) per os (PO), (b) intradoacal (CI), and (c) cloacal drop (CD). Feed restriction was also studied as a predisposing factor. Intracloacal inoculation (CI) consistently produced severe infections in all experiments. In several experiments, turkeys did not become infected after inoculation PO with 1 x 10(5) cultured histomonads. Feed restriction prior to inoculation did not make turkeys susceptible to infection inoculated PO. However, when liquid cultures containing histomonads were applied to the vent (CD) and the dorsal lip stimulated to initiate cloacal drinking, the histomonads were taken into the cloaca and transported to the ceca by retrograde peristalsis. Heavy infections were produced by this method, with severe liver and cecal lesions recorded when birds were necropsied 12 days later. These results suggest that CD may provide ready entry into the lower intestinal tract for these parasites and may facilitate spread of infection through flocks.     

Acaricidal activity of extract from Eupatorium adenophorum against the Psoroptes cuniculi and Sarcoptes scabiei in vitro

The possible acaricidal activity of Eupatorium adenophorum was analyzed using extracts created by water decocting, ethanol thermal circumfluence, and steam distillation. The toxic effect of each extract was tested against Psoroptes cuniculi and Sarcoptes scabiei in vitro. Ethanol thermal circumfluence extract had strong toxicity against mites, killing all S. scabiei at 0.5 and 1.0 g/ml (w/v) concentration, while 1g/ml extract was also found to kill all P. cuniculi within a 4-h period. Similarly, 0.25, 0.5 and 1.0 g/ml concentration of extract had strong toxicity against S. scabiei, with median lethal time (LT(50)) values at 0.866, 0.785 and 0.517 h, respectively. 0.5 g/ml and 1g/ml showed strong acaricidal action against P. cuniculi; the LT(50) values were 0.93 h and 1.29 h, respectively. The median lethal concentration (LC(50)) values were 0.22 g/ml for Scabies mite and 0.64 g/ml for P. cuniculi in 1h. The results indicated that E. adenophorum contains potent acaricidal ingredients; as a first step in the potential development of novel drugs, it may provide new acaricidal compounds for the effective control of animal acariasis.     

Evaluation of an implanted osmotic pump for delivery of amikacin to corn snakes (Elaphe guttata guttata).

The risk of accidental envenomation to the handler of venomous snakes during drug administration limits the ability to treat these animals. One commercially available osmotic pump is a miniature self-contained cylindrical implant that operates on the basis of an osmotic pressure difference between the extracellular fluid and the osmotic agent in the pump. Osmotic pumps loaded with amikacin were surgically placed into the coelomic cavity of five adult corn snakes (Elaphe guttata guttata) (group A). Four snakes (group B) received an intramuscular injection of amikacin at 5 mg/kg followed by 2.5 mg/kg q 72 hr for a total of four injections. Plasma concentrations of amikacin were measured in both groups. Renal function was evaluated pre- and posttreatment via scintigraphy with 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) and measurement of plasma uric acid concentrations. Mean (+/- SD) steady state amikacin concentration for group A was 6.9 +/- 1.7 microg/ml (predicted = 8.0 microg/ml), and the measured pump rate was 0.134 +/- 0.017 microl/hr (predicted = 0.130 microl/hr). Mean (+/- SD) peak and trough plasma amikacin concentrations for group B were 22.7 +/- 8.5 microg/ml and 14.3 +/- 7.0 microg/ml, respectively. While neither scintigraphy nor plasma uric acid concentrations indicated toxicity in either group, continuous administration of aminoglycosides may cause nephrotoxicity, and it is unknown whether this delivery method of amikacin would be efficacious in treating bacterial infections in snakes. In addition, due to migration of one pump into the trachea causing asphyxiation and death, these pumps may not be appropriate for intracoelomic placement in corn snakes. Nonetheless, the pumps delivered the drug at a predictable rate and were efficacious in achieving a constant plasma concentration of amikacin at the predicted level. Osmotic pumps may offer a safer alternative to periodic intramuscular injections for drug delivery in venomous or aggressive snakes.     

Plasma concentrations of oxytetracycline in swine after administration of the drug intramuscularly and orally in feed

Four pigs were used in a 2 X 2 crossover study to determine plasma oxytetracycline (OTC) concentration and OTC pharmacokinetic variables after IM administration of 2 OTC preparations--long acting OTC and a 100-mg of OTC/ml solution (OTC-LA and OTC-100, respectively)--at a dosage of 20 mg/kg of body weight. In a second study, 3 additional pigs were given ad libitum access to feed containing pure OTC (0.55 g/kg of feed). The mean (+/- SD) peak plasma OTC concentration after OTC-LA administration was 6.0 +/- 2.2 micrograms/ml at 30 minutes; the mean peak plasma OTC concentration after OTC-100 administration was 6.7 +/- 3.4 micrograms/ml at 90 minutes. Mean plasma OTC concentration after oral OTC administration in feed peaked at 0.4 micrograms/ml 48 hours after access to OTC-medicated feed and decreased to 0.25 micrograms/ml by the end of that study. Mean plasma OTC concentration was maintained at greater than 0.5 micrograms/ml for less than 48 hours after OTC-LA administration and for less than 36 hours after OTC-100 administration. Mean plasma OTC concentration decreased to less than 0.2 micrograms/ml by 72 hours after IM administration of either product. Calculation of area under the plasma OTC concentration-time curve (AUC) did not reveal significant difference between the 2 OTC formulations. There also was not significant difference (between OTC-LA and OTC-100) in the value of the disappearance rate constant after administration of either OTC formulation. The data did not indicate significant pharmacologic advantage of OTC-LA, compared with OTC-100, when either formulation was administered IM at a dosage of 20 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

肝素钠对伪狂犬病毒侵染BHK-21细胞和小白鼠的抑制

应用空斑技术,检测肝素钠对伪狂犬病毒（ＰＲＶ）在ＢＨＫ＿２１细胞上形成空斑的数量,证实肝素钠对ＰＲＶ的感染能力有较大抑制作用。小鼠试验证实肝素钠可降低病毒的致病力,但肝素钠对小鼠有一定毒性。     

Prenatal exposure to corticosterone impairs embryonic development and increases fluctuating asymmetry in chickens (Gallus gallus domesticus)

1. The level of corticosterone in fertilised eggs from hens (Gallus gallus domesticus) was manipulated experimentally to elucidate whether stress in laying hens is harmful to the chicks, as manifested by impaired survival and reduced growth, and whether bilateral asymmetry may represent an indicator of environmental stress in poultry. 2. Three hundred and fifty eggs were randomly divided into 4 groups; 1. untreated, 2. control, 3. 10 ng corticosterone/ml and 4. 20 ng corticosterone/ml. Each of the eggs in groups 2, 3 and 4 were injected with 100 microl ethanol-saline solution (25% ethanol in saline) containing 0, 0.6 and 1.2 microg corticosterone, respectively. After the injections, the final concentration of ethanol in the egg (albumen and yolk) was 0.03%, and the concentration of added corticosterone was 0, 10 and 20 ng/ml, respectively, in groups 2, 3 and 4. All the eggs were treated on developmental d 1. 3. Corticosterone injections resulted in greater embryonic mortality, earlier termination of foetal development and reduced growth. Moreover, chicks developing in eggs with an elevated concentration of corticosterone displayed reduced developmental stability as evidenced by increased fluctuating asymmetry (FA) in tarsus length. 4. In conclusion, an increased concentration of corticosterone in the egg was detrimental to survival and growth of the chicks. Prenatal stress also generated bilateral asymmetry, and illustrates the potential application of FA as an indicator of environmental stress in poultry.     

Synovial fluid analysis and bacterial findings in arthritic joints of juvenile male camel (Camelus dromedarius) calves

Eighteen synovial fluid samples from 11 male dromedarian calves, 9-12 month old, were analysed cytologically and bacteriologically. Calves were lame and all joints were grossly swollen. The mean +/- SD of total nucleated cell count was 7970 +/- 5000 cells/microl (range 2800-20,000 cells/microl). Polymorphonuclear (PMN) leucocytes were the predominant cell type. The mean +/- SD of absolute and percentages of each cell type were as follows: PMN leucocytes 5518 +/- 3600 cells/microl and 68 +/- 19%, monocytes/macrophages 1600 +/- 1120 cells/microl and 26 +/- 17%, lymphocytes 830 +/- 140 cells/microl and 8 +/- 7%, and red blood cell 350 +/- 130 cells/microl. The mean +/- SD of total protein concentration was 3.5 +/- 1 g/dl (range 2.5-5 g/dl). The most commonly isolated bacteria were non-haemolytic streptococci spp., followed by Arcanobacterium pyogenes and Staphylococcus aureus. No bacterial growth was obtained in eight samples and non-revealed Mycoplasma spp.     

Comparison of the serum pharmacokinetics of a long acting and a conventional oxytetracycline injection

A crossover study was carried out in cattle to determine the serum pharmacokinetics of a standard dose (20 mg/kg bodyweight) of oxytetracycline given either as a conventional injectable formulation or as a long acting formulation. For reference purposes, an intravenous treatment (also given at 20 mg/kg) was included in the trial protocol. A comparison of the two treatment regimes showed that the long acting formulation gave a significantly lower peak oxytetracycline serum concentration, with a significant extension of drug serum concentration. The long acting formulation also showed a longer serum half life and a significantly greater area under the curve value, calculated from 36 hours onwards, together with serum oxytetracycline concentrations which exceeded 0.5 microgram/ml for 86.8 as opposed to 51.5 hours for the conventional formulation. It is concluded that the use of the long acting formulation in cattle leads to a more sustained serum oxytetracycline concentration than does the same dose of conventional formulation.     

Effect of collection frequency on quantitative and qualitative characteristics of pigeon (Columba livia) semen

The aim was to estimate the optimal frequency of semen collection from pigeons in relation to ejaculate volume, sperm concentration, total spermatozoa in ejaculate and percentage of live morphologically normal cells. The study was carried out on 455 ejaculates collected from two groups of pigeons, each of 10 males (group I: meat-type breed; group II: fancy pigeon). The birds were selected and kept individually in cages under a natural photoperiod. A two-person technique was used for semen collection (lumbo-sacral and cloacal region massage). Semen was collected once, twice or three times per week. Colour, consistency and volume of ejaculates were evaluated macroscopically immediately after collection. Sperm concentration and total number of cells in the ejaculate were estimated after dilution with Ringer's solution. A live-dead stain technique (nigrosin-eosin) was used to determine the percentage of live and normal spermatozoa. Semen collected 3x/week was of high quality. The average volume of a single ejaculate was small (21 microl in group I and 19 microl in group II), but sperm concentration was high--1.58 x 10(9)/ml and 1.96 x 10(9)/ml, respectively. The mean number of spermatozoa per ejaculate was 30.48 x 10(6) in group I and 39.49 x 10(6) in group II. An increased percentage of live and normal spermatozoa in semen collected more frequently was also observed. Collecting pigeon semen 3x/week provides spermatozoa in larger amounts and of better quality than less frequent collections (1x/week or 2x/week) and is recommended for obtaining more insemination doses.     

Pharmacokinetics of Eprinomectin in Plasma and Milk following Subcutaneous Administration to Lactating Dairy Cattle

Eprinomectin is only available as a topically applied anthelmintic for dairy cattle. To determine whether eprinomectin can be applied as an injectable formulation in dairy cattle, a novel injectable formulation was developed and was subcutaneously delivered to four lactating dairy cattle at a dose rate of 0.2 mg/ kg. Plasma and milk samples were collected. The concentrations of eprinomectin in all samples were determined by HPLC. The peak plasma concentration (C_max)of 44.0±24.2 ng/ml occurred 39±19.3 h after subcutaneous administration, equivalent to the C_max (43.76±18.23 ng/ml) previously reported for dairy cattle after a pour-on administration of 0.5 mg/kg eprinomectin. The area under the plasma concentration–time curve (AUC) after subcutaneous administration was 7354±1861 (ng h)/ml, higher than that obtained after pour-on delivery (5737.68±412.80 (ng h)/ml). The mean residence time (MRT) of the drug in plasma was 211±55.2 h. Eprinomectin was detected in the milk at the second sampling time. The concentration of drug in milk was parallel to that in plasma, with a milk to plasma ratio of 0.16±0.01. The highest detected concentration of eprinomectin in milk was 9.0 ng/ml, below the maximum residue limit (MRL) of eprinomectin in milk established by the Joint FAO/WHO Expert Committee on Food Additives in 2000. The amount of eprinomectin recovered in the milk during this trial was 0.39%±0.08% of the total administered dose. This study demonstrates that subcutaneous administration of eprinomectin led to higher bioavailability and a lower dose than a pour-on application, and that an injectable formulation of eprinomectin may be applied in dairy cattle with a zero withdrawal period.     

C型产气荚膜梭菌合成培养基使用参数及培养毒素浓缩工艺优化

确定C型产气英膜梭菌合成培养基使用参数及建立配套的毒素浓缩工艺。比较不同pH值、灭菌温度、配制用水的合成培养基及其不同培养时间和温度下培养产气荚膜梭菌CVCC60102株的毒力;按毒素的分子量及超滤膜的截留分子量设计并比较2种不同浓缩工艺的毒素收获率及透出液的毒力。结果表明,pH值为8．0～8．4、灭菌方式为116℃30min、配制用水为去离子水时产毒最佳,毒力达到500—1000MLD／mL;合成培养基培养产气英膜梭菌CVCC60102株18h后毒力达500—1000MLD／mL,随着时间的延长,毒力不再增强;培养温度为36℃或37℃时,产毒效果最佳;不同截留分子量的超滤膜浓缩,10ku截留分子量的收获率为68％,其透出液静脉接种0．2mL,小鼠2／2死亡;而8ku收获率达80％,其透出液静脉接种0．2mL,小鼠0／2死亡。因此8ku截留分子量膜包适宜对C型菌培养毒素的浓缩。上述结果为C型产气荚膜梭菌合成培养基的应用提供了数据支撑。     

Hematology and serum biochemistry of free-ranging nutria (Myocastor coypus)

Information on reference blood values in the literature is lacking for many wild rodents. In this study, comprehensive reference intervals (RIs) for a wide range of analytes from 101 healthy free-ranging nutria were determined. Animals were captured in Buenos Aires, Argentina (37degrees 50'S, 57 degrees 34'W), and southward (38 degrees 60'S, 58 degrees 23'W), encompassing major biotopes of agricultural pampas with dunes and grassland steppes on the east coast. Traps were set at locations with high-density nutria populations (i.e., those areas that showed signs of movement, territorial marking, or feeding activities). Although the small sample size limits the interpretation of these findings, RIs were determined by a robust method using the central 95th percentile. In nutria, the RI range varied greatly for the leukocyte differentials, with mature neutrophils: 3,907-5,544/mmicrol for females and 3,744-5,900/microl for males; band neutrophils: 0-10/ll for females and 3-18/microl for males; lymphocytes: 4,213 5,940/microl for both sexes combined; monocytes: 165-402/microl for both sexes combined; eosinophils: 13-91/microl for females and 108-165/microl for males; and basophils: 0-87/microl for both sexes combined. Platelet concentration was 543-727 x 10(9)/L for both sexes combined. There was also a wide RI range for biochemistry values for some enzymes, such as alkaline phosphatase: 200-399 IU/L for both sexes combined; cholinesterase: 762-1,407 IU/L for females and 763-1,284 IU/L for males; creatine kinase: 182-552 IU/L for females and 162-451 IU/L for males; amylase: 853-1,865 IU/L for females and 779-1,293 IU/L for males; and glucose concentration 120.2-180.6 mg/dl for both sexes combined. Conversely, there was not a wide pooled RI range for calcium: 7.0-11.2 mg/dl; phosphorous: 6.1-9.3 mg/dl; sodium: 133.0-159.0 mEq/L; potassium: 3.0-8.2 mEq/L; chloride: 101.4-143.0 mEq/L; and urea: 11.3-36.8 mg/dl. The red blood cell indices had a narrow range, with mean corpuscular volume: 84.0 -102.5 fl and mean corpuscular hemoglobin concentration: 18.2-28.8 g/dl, and which was most likely due to strict physiologic controls. The results from this study were similar to those previously reported for farmed nutria.     

Transdermal absorption of a liposome-encapsulated formulation of lidocaine following topical administration in cats

OBJECTIVE: To determine plasma disposition after dermal application of a liposome-encapsulated formulation of lidocaine in cats. ANIMALS: 6 healthy adult cats with a mean (+/- SD) body weight of 4.1 +/- 0.44 kg. PROCEDURE: CBC determination and biochemical analysis of blood samples were performed for all cats. Cats were anesthetized by use of isoflurane, and catheters were placed IV in a central vein. The next day, blood samples were obtained from the catheters before and 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after applying a 4% liposome-encapsulated lidocaine cream (15 mg/kg) to a clipped area over the cephalic vein. Plasma concentrations of lidocaine were analyzed with a high-performance liquid chromatography assay. Results-Two cats had minimal transdermal absorption of lidocaine, with lidocaine concentrations below the sensitivity of the assay at all but 1 or 2 time points. In the other 4 cats, the median maximum plasma concentration was 149.5 ng/ml, the median time to maximum plasma concentration was 2 hours, and the median area under the concentration versus time curve from zero to infinity was 1014.5 ng.h/ml. CONCLUSIONS AND CLINICAL RELEVANCE: Maximum plasma concentrations of lidocaine remained substantially below toxic plasma concentrations for cats. On the basis of these data, topical administration of a liposome-encapsulated lidocaine formulation at a dose of 15 mg/kg appears to be safe for use in healthy adult cats.     

Acaricidal properties of the essential oil of Melaleuca alternifolia Cheel (tea tree oil) against nymphs of Ixodes ricinus

The aim of the study was to examine the acaricidal effect of essential oil of Melaleuca alternifolia (tea tree oil, TTO) at different doses (4, 6, 8 and 10 microl) and for different exposure times (30, 60, 90 and 120 min) on nymphs of Ixodes ricinus. A dose of 8 microl TTO was lethal for more than 70% of ticks when inhaled and this effect was enhanced when the dose was increased to 10 microl (> 80%). The effect was correlated with the duration of exposure of ticks to TTO, with a significant effect being observed after 90 min exposure. The findings show that TTO has acaricidal properties and could be extremely useful in controlling ticks that are efficient vectors of pathogens.     

Effects of blood contamination of cerebrospinal fluid on results of indirect fluorescent antibody tests for detection of antibodies against Sarcocystis neurona and Neospora hughesi.

The purpose of this study was to determine the effect of blood contamination of cerebrospinal fluid (CSF) on the results of indirect fluorescent antibody tests (IFATs) for Sarcocystis neurona and Neospora hughesi. The in vitro study used antibody-negative CSF collected from non-neurologic horses immediately after euthanasia and blood samples from 40 healthy horses that had a range of IFAT antibody titers against S. neurona and N. hughesi. Serial dilutions of whole blood were made in seronegative CSF to generate blood-contaminated CSF with red blood cell (RBC) concentrations ranging from 10 to 100,000 RBCs/microl. The blood-contaminated CSF samples were then tested for antibodies against both pathogens using IFAT. Blood contamination of CSF had no detectable effect on IFAT results for S. neurona or N. hughesi at any serologic titer when the RBC concentration in CSF was <10,000 RBCs/microl. At concentrations of 10,000-100,000 RBCs/microl of CSF, positive CSF results (IFAT titer >or=5) for S. neurona and N. hughesi were detected only when the corresponding serum titers were >or=160 and >or=80, respectively. The IFAT performed on CSF is reliable for testing horses for equine protozoal myeloencephalitis caused by S. neurona or N. hughesi, even when blood contamination causes the RBC concentration in CSF to be up to 10,000 RBCs/microl.     

Antimicrobial susceptibility of Riemerella anatipestifer isolated from ducks and the efficacy of ceftiofur treatment.

The in vitro susceptibilities of 50 field isolates of Riemerella anatipestifer from ducks to ceftiofur and 16 other commonly used antimicrobials were determined. The MIC90 values (MIC refers to minimum inhibitory concentrations) for the antimicrobials used in this study are as follows: penicillin was 16 microg/ml; ceftiofur was 32 microg/ml; cephalothin, chloramphenicol, flumequine, and kanamycin were 64 microg/ml; nalidixic acid, nitrofurantoin, and sulfamethoxazole were 128 microg/ml; amikacin, ampicillin, gentamicin, lincomycin, spectinomycin, streptomycin, tetracycline, and trimethoprim were > or = 256 microg/ml. The therapeutic efficacy of ceftiofur against a highly lethal experimental R. anatipestifer infection in ducks was also evaluated. All experimental ducks were infected through the infraorbital sinus with 1 ml of 9 x 10(9) CFU of R. anatipestifer. Ceftiofur (0, 0.25, 0.5, 1, and 2 mg/kg) was injected subcutaneously 5 hours after infection. A single dose of 2 mg/kg resulted in 73% survival as compared with 10% survival in the infected, but untreated controls.     

Comparative pharmacokinetics, bioavailability and renal clearance of five parenteral oxytetracycline-20% formulations in dairy cows

Oxytetracycline (OTC) concentrations on plasma and milk of dairy cows were determined following a single intramuscular injection of five oxytetracycline-20% formulations at a dosage of approximately 10 mg/kg. For obtaining pharmacokinetic reference parameters, one 10% OTC formulation was administered intravenously. The five 20% formulations were compared and evaluated pharmacokinetically with respect to absorption rate, peak plasma and milk OTC concentrations, biological half-life, and relative bioavailability. The mean maximum plasma OTC concentrations varied between 4.5 and 6.8 micrograms/ml and were achieved between 5 and 10 h p.i., depending on the formulation involved. The mean maximum milk concentrations, ranging from 1.12 to 1.92 micrograms/ml, were achieved 12 to 24 h p.i. A plasma OTC concentration exceeding 0.5 microgram/ml was maintained for 48 h to 70 h, and in milk for 33 to 49 h, depending on the formulation involved. Formulations exhibiting the lowest clinically noticeable irritation showed the highest peak plasma OTC concentrations and the best bioavailability. Among the formulations the calculated withholding periods for milk were in the range of 3 to 4 days and for edible tissues of 9 to 14 days. The OTC and creatinine clearances were significantly correlated to each other and to the urinary flow. OTC was excreted predominantly by glomerular filtration, partly by tubular secretion minus urogenital (distal renal tubuli and bladder) reabsorption.