Serum pharmacokinetics and tissue and milk residues of oxytetracycline in goats following a single intramuscular injection of a long-acting preparation and milk residues following a single subcutaneous injection

Separate groups of goats were used to determine drug depletion patterns in serum (n=10), tissue (n=20) and milk (n=8) following a single intramuscular (i.m.) dose of 20 mg/kg of a long-acting oxytetracycline (OTC) formulation (Liquamycin LA-200). Milk residues were also determined following a subcutaneous (s.c.) administration of the same product at the same dose. Serum samples were taken for 24 h post-treatment and tissues (fat, liver, kidney, muscle and injection site) collected at 4, 7, 14, 21 and 28 days following injection. Milk from lactating goats was collected every 12 h for 8 days following both the i.m. and s.c. treatments utilizing an intervening 5-week washout period. Residues in serum and tissue were measured using a microbial inhibition assay, while milk residues were measured using both a microbial inhibition assay and a validated HPLC method. The serum pharmacokinetic parameters of OTC in goats were determined, with a mean AUC=67.4 microg h/mL, mean terminal half-life=14.4 h, and apparent clearance=0.33 L/kg h. Tissue half-lives could not be determined with confidence because the collection times provided only two points at which residues could be measured for most tissues. Oxytetracycline residues in all goat tissue samples measured less then cattle tissue tolerance by 96 h postdosing. One-compartment model describing milk depletion data for i.m. and s.c. dosing had terminal slope half-lives of 20.1 and 36.1 h, respectively. By 96 h post-treatment none of the milk samples contained OTC residues in excess of the cattle milk tolerance (0.3 p.p.m.). For both milk and tissue, the upper-bound 99% confidence intervals for the samples taken from goats 96 h postdosing were lower than approved cow milk and tissue tolerances.     

Pharmacokinetics of amikacin in pony foals after a single intramuscular injection

Six healthy pony foals, from 2 to 11 days of age, were given a single IM injection of amikacin sulfate (250 mg/ml) at a dosage rate of 7 mg/kg of body weight. Serum amikacin concentrations were measured serially over a 24-hour period. The mean peak serum concentration was 14.7 micrograms/ml at 0.5 hour. The elimination rate constant for amikacin was 0.24/hour, the elimination half-life was 3.0 hours, and the apparent volume of distribution was 0.58 L/kg.     

Fate and residues of [4-14C]estradiol-17 beta after intramuscular injection into Holstein steer calves

Radiocarbon-labeled estra-1,3,5(10)-triene-3,17 beta-diol [4-14C-estradiol-17 beta; beta-estradiol] was suspended in commercial peanut oil and administered to each of three Holstein steer calves (142 to 170 kg body weight) by deep injection into neck muscle via 2.0 ml peanut oil carrier. The dosages were equivalent to .27 to .29 mg beta-estradiol/kg body weight. After dosing, radiocarbon was rapidly and almost totally eliminated in urine and feces. Most of the administered radiocarbon had been eliminated after 2 d, and by 11 d after treatment no radiocarbon was detectable in urine or feces of any calf. Of the total dose, 42.1 +/- 3.8% was excreted in urine and 57.7 +/- 5.2% was eliminated in feces. Analysis of noninjection site tissue samples (blood, brain, fat, kidney, liver and muscle) collected at sacrifice 14 d after treatment showed that none contained detectable radiocarbon residues, with the sensitivity limit for most tissues being 6 ppb beta-estradiol equivalent. Certain sections of muscle taken from the injection site area did contain detectable radiocarbon residues (as much as 69 ppb beta-estradiol equivalent), but total injection site area residues in each calf comprised less than .07% of the total administered dose. Radiocarbon in urine consisted primarily of alpha-estradiol, with much lesser amounts of estrone. Both compounds occurred as nonconjugates and as glucuronides. beta-Estradiol was not detected in urine. Radiocarbon in feces included primarily alpha-estradiol but also beta-estradiol and estrone, each in non-conjugated form. The fact that most of the intramuscular-administered beta-estradiol was eliminated in the feces strongly suggests a major role for biliary excretion in the disposition of this steroid by steer calves.     

Population pharmacokinetics of ceftazidime after a single intramuscular injection in wild turtles

Ceftazidime, a third‐generation cephalosporin, is important for treating opportunistic bacterial infections in turtles. Antibacterial dosage regimens are not well established for wild turtles and are often extrapolated from other reptiles or mammals. This investigation used a population pharmacokinetic approach to study ceftazidime in wild turtles presented for rehabilitation. Ceftazidime was administered to 24 wild turtles presented to the Turtle Rescue Team at North Carolina State University. A sparse blood sampling protocol was used to collect samples from 0 to 120 hr with three samples per individual after injection. Plasma samples were analyzed by high‐pressure liquid chromatography (HPLC). A nonlinear mixed‐effects model (NLME) was fitted to the data to determine typical values for population parameters. We identified a long half‐life (T½) of approximately 35 hr and volume of distribution (V_SS) of 0.26 L/kg. We concluded that this long T½ will allow for a dose of 20 mg/kg injected IM to maintain concentrations above the MIC of most wild‐type bacteria for 5 days. Because of long intervals between injections, stability of stored formulations was measured and showed that 90% strength was maintained for 120 hr when stored in the refrigerator and for 25 days when stored in the freezer.     

Herd tests on meat livestock to protect consumers from zoonotic pathogens and chemical residues

Clinical veterinary work is of prime importance for the task of the veterinary food hygienist. This is particularly true of early clinical, allergological, serological and bacteriological examination of herds of meat livestock, as proposed by Bartels, Kampelmacher, Grossklaus and others. Such investigations would make it possible to diagnose latent types of zoonosis which would otherwise remain undetected during official meat inspection. The pathological and anatomical findings during meat inspection are also of clinical importance. To these must be added the necessary measures to eliminate toxicologically significant residues of pharmacologically active substances. On the basis of his own research the author presents proposals for herd tests which could help to promote, with improved safety, international trade in animal products for human consumption.

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Kurzfassung Die klinische Tätigkeit des Tierarztes beeinflusst wesentlich die Arbeit des tierärztlichen Lebensmittelhygienikers. Dies trifft besonders für die rechtzeitige klinische, allergologische, serologische und bakteriologisch-virologische Untersuchung von Schlachttieren in ihren Beständen zu, wie sie u. a. von Bartels, Kampelmacher und Grossklaus vorgeschlagen wurde. Sie soll u.a. die Diagnose inapparent verlaufender Zoonosen ermöglichen, die sonst im Rahmen der amtlichen Fleischuntersuchung unerkannt bleiben. Der pathologisch-anatomische Befund aus der Fleischuntersuchung ist zudem wichtig für den Kliniker. Hinzu kommen erforderliche Massnahmen zur Ausschaltung von toxikologisch relevanten Rückständen pharmakologisch wirksamer Substanzen. Anhand eigener Untersuchungen werden Vorschläge für sog. Bestandsuntersuchungen unterbreitet die in der Lage sein könnten, den internationalen Handel mit vom Tier stammenden Lebensmitteln sicherer zu gestalten und zu fördern.

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Resume L'action du vétérinaire praticien a une influence primordiale sur le travail du vétérinaire hygiéniste. Cela est particulièrement vrai pour l'examen clinique, allergologique, sérologique et bactériologique des animaux de boucherie, au niveau des élevages, proposé par des auteurs comme Bartels, Kampelmacher et Grossklaus. Il doit rendre possible le diagnostic des zoonoses inapparentes qui risqueraient de passer inapercues au stade de l'inspection des viandes. Du reste, le diagnostic anatomo-pathologique résultant de l'inspection des viandes est important pour le clinicien. Il faut ajouter les mesures nécessaires pour éliminer les résidus toxiques provenant de substances pharmacologiques actives. En se basant sur ses propres études, l'auteur fait des propositions pour des examens dits des troupeaux qui pourraient rendre plus sûr et plus efficace le commerce international des dentées d'origine animale.

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Riassunto L'attività del medico veterinario influenza sensibilmente il lavoro dell'igenista veterinario-alimentare. Questo vale in particolare per l'esame clinico, allergico, sierologico e batteriologico degli animali da macello negli allevamenti, proposti da autori quali Bartels, Kampelmacher e Grossklaus. Gli esami debbono permettere la diagnosi delle zoonosi inapparenti che rischierebbero di passare inosservate in fase di ispezione delle carni. Pertanto la diagnosi anatomo-patologica risultante dall'ispezione delle carni è importante anche per il clinico. A cio' si devono aggiungere misure atte ad eliminare i residui tossici provenienti dalle sostanze farmacologiche attive. Basandosi sui suoi studi, l'autore fa proposte relative agli esami detti di mandria che potrebbero rendere più sicuro e efficace il commercio internazionale degli alimenti di origine animale.

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This article was originally written in German. Copies of the German version may be obtained free of charge by writing to: Mr. J. Rodesch, Commission of the European Communities, DG XIII, Bâtiment Jean Monnet, Rue Alcide de Gasperi, Kirchberg, Luxembourg.     

Pharmacokinetics of enrofloxacin after intravenous and intramuscular injection in rabbits.

The pharmacokinetics and bioavailability of enrofloxacin were determined after IV and IM administration of 5 mg/kg of body weight to 6 healthy adult rabbits. Using nonlinear least-squares regression methods, data obtained were best described by a 2-compartment open model. After IV administration, a rapid distribution phase was followed by a slower elimination phase, with a half-life of 131.5 +/- 17.6 minutes. The mean body clearance rate was 22.8 +/- 6.8 ml/min/kg, and the mean volume of distribution was 3.4 +/- 0.9 L/kg. This large volume of distribution and the K12/K21 ratio close to 1, indicated that enrofloxacin was widely distributed in the body, but not retained in tissues. After a brief lag period (6.2 +/- 2.86 min), IM absorption was rapid (4.1 +/- 1.3 min) and almost complete. The mean extent of IM absorption was 92 +/- 11%, and maximal plasma concentration of 3.04 +/- 0.34 micrograms/ml was detected approximately 10 minutes after administration.     

Serum pharmacokinetics of oxytetracycline in sheep and calves and tissue residues in sheep following a single intramuscular injection of a long-acting preparation

The pharmacokinetics of a long‐acting oxytetracycline (OTC) formulation (Liquamycin® LA‐200®) injected intramuscularly (i.m.) at a dose of 20 mg/kg were determined in four calves and 24 sheep to determine if the approved label dose for cattle provided a similar serum time/concentration profile in sheep. The AUC for the calves was 168±14.6 (μg ? h/mL) and was significantly less than the AUC for sheep (209±43 μg ? h/mL). Using the standard two‐stage approach and a one‐compartment model, the mean Cmax for the calves was 5.2±0.8 μg/mL, and for the sheep was 6.1±1.3 μg/mL. The mean terminal phase rate constants were 0.031 and 0.033 h, and the Vdss were 3.3 and 3.08 L/kg for the calves and sheep respectively. Analysis of the data using the standard two‐stage approach, the naive pooled‐data approach and a population model gave very similar results for both the cattle and sheep data. Sheep tissue residues of OTC in serum, liver, kidney, fat, muscle and injection site were measured at 1, 2, 3, 5, 7 and 14 days after a single i.m. injection of 20 mg/kg OTC. Half‐lives of OTC residues in the tissues were 38.6, 33.4, 28.6, 25.4, 21.3, and 19.9 h for injection site, kidney, muscle, liver, mesenteric fat and renal fat, respectively. The ratio of tissue to serum concentration was fairly consistent at all slaughter times, except for the fat and injection sites. The mean ratios were 1.72, 4.19, 0.11, 0.061, 0.84 and 827 for the liver, kidney, renal fat, mesenteric fat, muscle and injection sites, respectively. The tissue concentrations of OTC residues were below the established cattle tolerances for OTC in liver (6 p.p.m.), muscle (2 p.p.m.) and kidney (12 p.p.m.) by 48 h, and in injection site muscle by 14 days after the single i.m. injection of 20 mg/kg.     

Application of diethylstilbestrol dipropionate in bulls. I. Excretion of residues in urine and faeces and histological and immunohistochemical changes in the prostate

In this experiment 20 one year old bulls received a single intramuscular injection of the anabolic preparation diethylstilbestrol dipropionate (DES-DP) (an oil preparation or an emulsion). Four animals received a corresponding placebo. The application of DES-DP to bulls caused characteristic histological alterations in the peripheral glandular epithelium of the prostate, which could be observed until four weeks after treatment. The value of histological investigation as a screening method was, however, limited by the occurrence of only few metaplastic lesions and a rapid recovery. By contrast, immunohistochemistry using a polyclonal cytokeratin antiserum K40 appeared to be a specific and very sensitive method to detect oestrogen-induced lesions in the prostate. In only two animals, six weeks after injection with the DES-emulsion, false-negative results were obtained, demonstrating the potential value of this screening method. The excretion of DES in the urine and faeces was monitored using radioimmunoassay following chromatographic purification of the urine and faeces extracts. The excretion of DES in urine was faster for animals of the oil group. The DES content in urine decreased to the 1 microgram/l level after 42 days (emulsion group) or 70 days (oil group). The excretion in faeces was comparable to that in urine. After day 21 the excretion patterns of the two excreta were indistinguishable.     

Evaluation of local and systemic immune responses induced by intramuscular injection of a Mycoplasma hyopneumoniae bacterin to pigs

OBJECTIVE: To evaluate immune responses induced by administration of Mycoplasma hyopneumoniae bacterin to pigs. Animals-60 healthy 7- to 10-day-old cross-bred boars. PROCEDURE: Pigs were assigned to 1 of 4 pig groups (15 pigs/group): vaccinated, challenged; vaccinated, nonchallenged; nonvaccinated, challenged; nonvaccinated, nonchallenged. Vaccinated pigs received IM injections of a mycoplasma bacterin on days 0 and 14, whereas nonvaccinated pigs received saline (0.9% NaCl) solution. Pigs in the challenged groups were inoculated intratracheally with M hyopneumoniae on day 42. Pigs were euthanatized and necropsied 41, 44, 48, and 70 days after the first vaccination, and proportion of lung surface with pneumonic lesions was determined. Percentage of lymphocyte subpopulations and number of interferon-gamma (IFN-gamma) secreting lymphocytes in blood and tissues, cytokine and antibody concentrations in bronchoalveolar lavage (BAL) fluid, and serum antibody concentrations were determined. RESULTS: Vaccination against and infection with M hyopneumoniae induced a local mucosal immune response in the respiratory tract of pigs. Proportion of lung surface with pneumonic lesions in vaccinated challenged pigs was reduced on day 70, compared with nonvaccinated challenged pigs. Vaccination stimulated the production of M hyopneumoniae-specific IFN-gamma secreting blood lymphocytes. Tumor necrosis factor-alpha concentration in BAL fluid on day 70 was increased in nonvaccinated challenged pigs, compared with vaccinated challenged pigs. CONCLUSIONS AND CLINICAL RELEVANCE: Vaccination against M hyopneumoniae induced local, mucosal, humoral, and cellular immune responses. Moreover, vaccination reduced the severity of lung lesions in challenged pigs, suggesting that mucosal antibodies, mediation of the inflammatory response, and cell-mediated immune responses are important for control of mycoplasmal pneumonia in pigs.     

Tissue damage and concentration at the injection site after intramuscular injection of chemotherapeutics and vehicles in pigs.

Intramuscular injection sites were examined for macroscopical and microscopical changes and for residues of drugs six and 30 days after injection of chemotherapeutic preparations or vehicles in swine. The chemotherapeutic preparations contained sulphonamide and/or trimethoprim. All the chemotherapeutic preparations and the vehicles except physiological saline and sterile water caused macroscopical and microscopical changes, mainly appearing as areas of necrotic muscle tissue six days after the injection and as scar tissue 30 days after the injection. Residues of drugs were found at nearly all the injection sites six days after the injection, while 30 days after the injection only residues of sulphonamides were detectable in nearly half of the injection sites.     

Pharmacokinetics and tissue residues of gentamicin in lactating cows after multiple intramuscular doses are administered

Gentamicin was administered IM to 6 healthy, mature, lactating cows at a dosage of 3.5 or 5 mg/kg of body weight every 8 hours for 10 consecutive days (total, 30 doses). Endometrial biopsies were done at 72, 136 or 144, and 216 hours after the first dose was administered. On the 10th day, just before the last dose of gentamicin was administered, blood samples (designated 10th-day base-line samples) were obtained, and serial blood samples were obtained for 144 hours after the last injection was given. The cows were catheterized on the 10th day, and urine was obtained for 10 to 18 consecutive hours. Milk samples were also obtained. The cows were slaughtered at different times after the last dose was given, and samples were taken from 22 tissues and organs. Serum, milk, urine, and tissue gentamicin concentrations were determined by radioimmunoassay. Serum gentamicin concentrations were best fitted to a 2-compartment open model. The mean half-lives for absorption, distribution, and elimination were 0.16 +/- 0.14, 2.59 +/- 0.53, and 44.91 +/- 9.38 hours, respectively. Total body clearance and renal clearance were 1.65 +/- 0.69 and 1.32 +/- 0.25 ml/min/kg, respectively. The percentage of the dose excreted unchanged in the urine at 8 hours after the last dose was given was 98 +/- 15. As expected, of the tissues examined, the gentamicin concentrations in the kidney cortex and medulla were 1,500 times greater than those in serum. Renal function remained within the baseline range during the 10 days of gentamicin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

An evaluation of calf castration by intra-testicular injection of a lactic acid solution

This experiment evaluated intra-testicular injection of a sclerosing drug, lactic acid, for castration of bulls. Its use was compared in 58 Brahman cross calves (50 to 128kg) with the general practice of open surgical castration. Chemical castration appeared to be more painful than surgical castration, though post-operative swelling and pain appeared similar for both methods. Chemical castration took 3 times longer than surgical castration (58 sec v 20 sec; P less than 0.01). Scrotal necrosis occurred in 25% of chemically-castrated calves and appeared due to drug leakage from the testes under the high pressure of injection. Healing time for chemical castrates was approximately twice that for surgical castrates. Five chemically-castrated calves (18%) retained one testis. Though all 5 were rendered sterile, each maintained androgenesis. This led to secondary male behaviour which caused management problems. Castration method did not influence post-operative growth. It is concluded that lactic acid administration is not a suitable alternative to the open surgical technique for castration of Brahman cross calves.     

Efficacy of intramuscular treatment of beef cows with oxytetracycline to reduce mastitis and to increase calf growth

Spring-calving multiparous Angus x Hereford cows were used to determine the efficacy of intramuscular treatment with oxytetracycline to reduce the incidence of mastitis-causing bacteria, decrease milk somatic cell counts (SCC), and increase calf growth. During 2 yr, milk samples were collected from each quarter from a total of 319 cows at 8 to 14 d after calving and at weaning, to determine the presence of bacteria and SCC. A California mastitis test (CMT) was performed on milk from each quarter of each cow at the initial sample collection. Cows with a CMT score of 1, 2, or 3 in at least one quarter, were randomly assigned to receive either an intramuscular injection of oxytetracycline (n = 63) or the control vehicle (n = 60), and cows with a CMT score of 0 or trace in all four quarters were not treated (n = 196). Calf weights were determined at birth, early lactation, and weaning. The number of somatic cells in milk and the percentage of quarters that were infected increased as CMT score increased (P < 0.01). The presence of mastitis-causing bacteria at calving increased (P < 0.05) the incidence of infection at weaning. The presence of mastitis-causing bacteria at weaning was associated with increased SCC for quarters and average SCC for cows (P < 0.01). Average SCC per cow at weaning increased (P < 0.05) as the number of infected quarters per cow increased. Treatment did not alter (P > 0.10) the percentage of cows or quarters infected with mastitis-causing bacteria or SCC of cows or quarters at weaning. Average SCC per cow was negatively correlated (P < 0.05) with calf weights at early lactation, but not with weaning weights of calves. Treatment did not influence (P > 0.10) calf weights at early lactation or at weaning. Cows with one or more dry quarters after calving had calves that weighed less at early lactation and weaning than cows with four functional quarters (P < 0.01). Intramuscular oxytetracycline treatment of beef cows that had CMT scores of 1 or greater after calving did not reduce intramammary infection rates or increase calf weights at weaning.     

Pharmacokinetics and tissue distribution of enrofloxacin after single intramuscular injection in Pacific white shrimp

The pharmacokinetic properties and tissue distribution of enrofloxacin (EF) were investigated after single intramuscular (i.m.) dose of 10 mg/kg body weight (b.w.) in Pacific white shrimp at 22 to 25°C. EF and its metabolite ciprofloxacin (CF) were determined by high‐performance liquid chromatography. After i.m. administration, EF was absorbed quickly, and the peak of EF concentration (C_max) reached at first time point in hemolymph. The volume of distribution V_d(area) of EF was 3.84 L/kg, indicating that the distribution of EF was good. The area under the concentration–time curve (AUC) of EF was 90.1 and 274.2 μg hr/ml in muscle and hepatopancreas, respectively, which was higher than 75.8 μg hr/ml in hemolymph. The EF elimination was slow in muscle and hepatopancreas with the half‐life (T_1/2β) of 52.3 and 75.8 hr, respectively. CF, the mainly metabolite of EF, was detected in hemolymph, muscle and hepatopancreas. The C_max was 0.030, 0.013 and 0.218 μg/ml, respectively. Based on a minimum inhibitory concentration (MIC) of 0.006–0.032 μg/ml for susceptible strains, EF i.m. injected at a dose 10 mg/kg could be efficacious against common pathogenic bacteria of Pacific white shrimp.     

Comparison of plasma pharmacokinetics and bioequivalence of ceftiofur sodium in cattle after a single intramuscular or subcutaneous injection

Ceftiofur sodium, a broad-spectrum cephalosporin, is active against gram-positive and gram-negative pathogens of veterinary importance. This study was designed to compare the bioequivalence of the sodium salt in cattle after a single intramuscular (i.m.) or subcutaneous dose (s.c.) of 2.2 mg ceftiofur equivalents/kg body weight. The criteria used to evaluate bioequivalence were (1) the area under the curve from time of injection to the limit of quantitation (LOQ) of the assay (AUC0-LOQ), and (2) time concentrations remained above 0.2 microg/mL (t>0.2). Twelve crossbred beef cattle were enrolled in a three-period, two-treatment crossover trial, with a minimum 2-week washout period between doses of 2.2 mg ceftiofur equivalents/kg. Blood samples were collected serially for up to 72 h post-injection. Plasma samples were then analyzed using a validated assay that measures ceftiofur, and all desfuroylceftiofur-related metabolites, by high-performance liquid chromatography (HPLC) as the stable derivative, desfuroylceftiofur acetamide. A maximum plasma concentration (Cmax) of 13.9+/-3.55 microg/mL was observed from 0. 67-2.0 h after i.m. administration, whereas a Cmax of 13.6+/-3.85 microg/mL was observed from 0.67-3.0 h after s.c. administration. The AUC0-LOQ was 108+/-35.0 microg. h/mL after i.m. dosing, compared with 105+/-29.8 microg. h/mL after s.c. dosing. The pre-established criterion for equivalence of the AUC0-LOQ for the i.m. and s.c. routes of administration was satisfied. The t>0.2 was 49.2+/-8.55 h after i.m. administration, compared with 47.0+/-9.40 h after s.c. administration. The pre-established criterion for equivalence of the t>0.2 for i.m. and s.c. administration was satisfied. The equivalence of AUC0-LOQ and t>0.2 for i.m. and s.c. administration of 2.2 mg ceftiofur equivalents (CE)/kg doses of ceftiofur sodium suggest similar therapeutic efficacy and systemic safety for the two routes of administration.     

Vaccination of the dam by the intramuscular or deep subcutaneous route to prevent neonatal calf enteric colibacillosis.

Comparison of colostrum-induced immunities in calves was made by challenge exposure with Escherichia coli. These calves were delivered of cows which were vaccinated intramuscularly or deep subcutaneously (in the region of the mammary lymph nodes) with strain B44 E coli bacterin during the last trimester of pregnancy. The calf of each cow was allowed to nurse colostrum naturally after birth. Cows vaccinated by either route of administration were capable of providing increased resistance to their calves, via the colostrum, when compared with nonvaccinated cows.     

Comparison of plasma pharmacokinetics and bioavailability of ceftiofur sodium and ceftiofur hydrochloride in pigs after a single intramuscular injection

Ceftiofur sodium, a broad-spectrum cephalosporin, is active against gram-positive and gram-negative pathogens of veterinary importance. Two studies were designed to compare the intramuscular bioavailability of the current sodium salt and the new hydrochloride salt in pigs at doses of either 3 mg or 5 mg ceftiofur equivalents (CE)/kg body weight. Twenty-six healthy young pigs were selected for these two-period, two-treatment crossover studies, 12 for the 3 mg/kg study and 14 for the 5 mg/kg study. Each animal received one intramuscular (i.m.) injection of ceftiofur sodium and one i.m. injection of ceftiofur hydrochloride with a 14-day washout period between the two treatments. Blood samples were collected serially for up to 96 h postinjection. Plasma samples were then analysed using a validated assay that measures ceftiofur and all desfuroylceftiofur-related metabolites by high-performance liquid chromatography. In the 3 mg/kg dosage study, average maximum plasma concentration (C(max)) after administration of ceftiofur sodium was 15.8+/-3.40 microg/mL at 0.4-4 h after injection. After administration of ceftiofur hydrochloride, the C(max) was 11.8+/-1.67 microg/mL at 1-4 h after injection. Concentrations of ceftiofur and metabolites 72 h after the injection were 0.392+/-0.162 microg/mL for ceftiofur hydrochloride and 0.270+/-0.118 microg/mL for ceftiofur sodium. The mean area under the curve (AUC), from time 0 to the limit of quantitation (AUC(O-LOQ)) after ceftiofur hydrochloride administration, was 216+/-28.0 microg x h/mL, compared to 169+/-45.4 microg x h/mL after ceftiofur sodium administration. The calculated time during which plasma concentrations remained above 0.02 microg/mL (t(>0.2)) was 85.3+/-10.6 h for ceftiofur sodium and 77.2+/-10.7 h for ceftiofur hydrochloride. In the 5 mg/kg dosage study, C(max) after administration of ceftiofur sodium was 28.3+/-4.45 microg/mL at 0.33-2 h after injection. After administration of ceftiofur hydrochloride, the C(max) was 29.7+/-6.72 microg/mL at 0.66-2 h after injection. Concentrations of ceftiofur and metabolites 96 h after the injection were 0.274+/-0.0550 microg/mL for ceftiofur hydrochloride and 0.224+/-0.0350 microg/mL for ceftiofur sodium. The mean AUC(O-LOQ) after ceftiofur hydrochloride administration was 382+/-89.8 microg x h/mL compared to 302+/-54.4 microg x h/mL after ceftiofur sodium administration. The t(>0.2) was 78.9+/-9.65 h for ceftiofur sodium and 94.2+/-8.64 h for ceftiofur hydrochloride. Based on the similarity of the pharmacokinetic parameters of the sodium and hydrochloride formulations of ceftiofur, similar therapeutic efficacy can be inferred for the two products.     

苜蓿草地土壤氮素有效性的化学与生物测试方法比较

摘要：以半干旱区5龄和9龄紫花苜蓿(Medicago sativa cv.Longdong)土壤为供试对象,采用3种提取剂（0.01 mol/L CaCl2,热水和1 mol/L KCl）结合黑麦草(Lolium perenne)盆栽的生物测试对2个年龄苜蓿地土壤有效氮供应能力进行测定。结果表明,0.01 mol/L CaCl2提取剂对硝态氮的提取能力显著高于热水和1 mol/L KCl,1 mol/L KCl提取土壤铵态氮的提取能力最小;黑麦草在5龄和9龄苜蓿土壤中的吸氮量分别为2 100和3 100 mg/m2,由0.01 mol/L CaCl2、热水和1 mol/L KCl提取剂提取的土壤硝态氮含量与黑麦草吸氮量呈显著正相关关系,均可反映土壤供氮能力,0.01 mol/L CaCl2、热水和1 mol/L KCl提取剂提取的土壤铵态氮含量与植物吸氮量关系不确定,不能作为反映土壤供氮能力的指标。