Pharmacokinetic profiles of metamizole (dipyrone) active metabolites in goats and its residues in milk

Metamizole (dipyrone, MET) is a nonopioid analgesic drug commonly used in human and veterinary medicine. The aim of this study was to assess two major active metabolites of MET, 4‐methylaminoantipyrin (MAA) and 4‐aminoantipyrin (AA), in goat plasma after intravenous (IV) and intramuscular (IM) administration. In addition, metabolite concentration in milk was monitored after IM injection. Six healthy female goats received MET at a dose of 25 mg/kg by IV and IM routes in a crossover design study. The blood and milk samples were analyzed using HPLC coupled with ultraviolet detector and the plasma vs concentration curves analyzed by a noncompartmental model. In the goat, the MET rapidly converted into MAA and the mean maximum concentration was 183.97 μg/ml (at 0.08 hr) and 51.94 μg/ml (at 0.70 hr) after IV and IM administration, respectively. The area under the curve and mean residual time values were higher in the IM than the IV administered goats. The average concentration of AA was lower than MAA in both groups. Over 1 μg/ml of MAA was found in the milk (at 48 hr) after MET IM administration. In conclusion, IM is considered to be a better administration route in terms of its complete absorption with long persistence in the plasma. However, this therapeutic option should be considered in light of the likelihood of there being milk residue.     

Comparison of milk and plasma pharmacokinetics of meloxicam in postpartum versus mid‐lactation Holstein cows

The objective of this study reported here was determine whether differences occurred in meloxicam pharmacokinetics between postpartum cows and mid‐lactation cows. Preliminary data from a separate study (P. J. Gorden, unpublished data) in postpartum cows demonstrated elevated plasma and milk concentration profiles compared to previously published data (Malreddy, Coetzee, KuKanich, & Gehring, 2013 ). Two different groups were enrolled, each with 10 cows. The treatment group (TRT) was postpartum cows treated with meloxicam, and the positive control (PC) group was cows in mid‐lactation treated with meloxicam. Plasma and milk meloxicam concentrations between the TRT and PC group were compared. Significant differences in meloxicam concentration in plasma were determined at all time points from 8 hr to 120 hr post‐treatment. In milk, there was a treatment (p = .003), time (p < .001), and treatment by time interaction (p < .001). Significant differences in milk meloxicam concentration were determined at all time points from 8 hr to 96 hr post‐treatment, except for the 16‐hr time point. The time needed for meloxicam to no longer be detected in milk of the TRT group was longer compared to the PC group, indicating that a longer milk withdrawal is needed. These data suggest higher bioavailability as the underlying mechanism. Further research is needed to determine the mechanisms underlying differences this outcome.     

Correlation between oral fluid and plasma oxytetracycline concentrations after intramuscular administration in pigs

The penetration of oxytetracycline (OTC) into the oral fluid and plasma of pigs and correlation between oral fluid and plasma were evaluated after a single intramuscular (i.m.) dose of 20 mg/kg body weight of long‐acting formulation. The OTC was detectable both in oral fluid and plasma from 1 hr up to 21 day after drug administration. The maximum concentrations (C_max) of drug with values of 4021 ± 836 ng/ml in oral fluid and 4447 ± 735 ng/ml in plasma were reached (T_max) at 2 and 1 hr after drug administration respectively. The area under concentration–time curve (AUC), mean residence time (MRT) and the elimination half‐life (t_1/2β) were, respectively, 75613 ng × hr/ml, 62.8 hr and 117 hr in oral fluid and 115314 ng × hr/ml, 31.4 hr and 59.2 hr in plasma. The OTC concentrations were remained higher in plasma for 48 hr. After this time, OTC reached greater level in oral fluid. The strong correlation (r = .92) between oral fluid and plasma OTC concentrations was observed. Concentrations of OTC were within the therapeutic levels for most sensitive micro‐organism in pigs (above MIC values) for 48 hr after drug administration, both in the plasma and in oral fluid.     

Disposition of ampicillin trihydrate in plasma,uterine tissue,lochial fluid,and milk of postpartum dairy cattle

The objective of this study was to determine the disposition of ampicillin in plasma, uterine tissue, lochial fluid, and milk of postpartum dairy cattle. Ampicillin trihydrate was administered by intramuscular (i.m.) injection at a dose of 11 mg/kg of body weight every 24 h (n = 6, total of 3 doses) or every 12 h (n = 6, total of 5 doses) for 3 days. Concentrations of ampicillin were measured in plasma, uterine tissue, lochial fluid, and milk using HPLC with ultraviolet absorption. Quantifiable ampicillin concentrations were found in plasma, milk, and lochial fluid of all cattle within 30 min, 4 h, and 4 h of administration of ampicillin trihydrate, respectively. There was no significant effect of dosing interval (every 12 vs. every 24 h) and no significant interactions between dosing interval and sampling site on the pharmacokinetic variable measured or calculated. Median peak ampicillin concentration at steady‐state was significantly higher in lochial fluid (5.27 μg/mL after q 24 h dosing) than other body fluids or tissues and significantly higher in plasma (3.11 μg/mL) compared to milk (0.49 μg/mL) or endometrial tissue (1.55 μg/mL). Ampicillin trihydrate administered once daily by the i.m. route at the label dose of 11 mg/kg of body weight achieves therapeutic concentrations in the milk, lochial fluid, and endometrial tissue of healthy postpartum dairy cattle.     

Pharmacokinetics of toltrazuril and its metabolites in pregnant and nonpregnant ewes and determination of their concentrations in milk,allantoic fluid,and newborn plasma

The objectives of this study were to determine the pharmacokinetics of toltrazuril and its metabolites in pregnant and nonpregnant ewes following a single oral dose and to determine the plasma concentrations of these compounds in milk, allantoic fluid, and newborn plasma. Eighteen healthy ewes were randomly divided into three groups (n = 6 each): pregnant ewes at 12–13 weeks of gestation (group A), nonpregnant ewes (group B), and pregnant ewes at 1–2 weeks before expected lambing date (group C). Ewes in all groups received a single oral dose of toltrazuril at 20 mg/kg body weight. In groups A and B, blood samples were collected at 1, 3, 5, 7, 9, 12, 15, 18 hr, every 6 hr to day 3, every 12 hr to day 7 and thereafter every 24 hr to day 14 post-toltrazuril administration. In group C, parturition was induced 24–36 hr after toltrazuril administration then milk, allantoic fluid, and newborn plasma samples were collected immediately after birth. Drug metabolites were assayed using ultra high-performance liquid chromatography–ultraviolet detection method (UHPLC-UV). The maximum concentration (C_max), area under the plasma concentration-time curve (AUC_0–t), AUC to 24 and 48 hr (AUC_0–24), and (AUC_0–48) were significantly higher in pregnant ewes. Longer apparent half-life (T_1/2), significantly higher apparent volume of distribution (Vd/F) and total clearance (Cl/F) were observed in nonpregnant ewes. The time to maximum plasma concentration (T_max), mean residence time (MRT) and elimination rate constant (K_el) were similar in both groups. The AUC_0–24 and AUC_0–48 were significantly higher in nonpregnant ewes. The AUC_0–t was significantly higher in pregnant ones. The ratio of plasma toltrazuril concentrations in ewes and toltrazuril concentrations in newborn lambs' plasma, allantoic fluid, and milk were 68%, 2.3%, and 5.3%, respectively. Results of this study showed that toltrazuril is well absorbed after a single oral dose in ewes with widespread distribution in different body tissues.     

Effects of continuous low dose infusion of lipopolysaccharide on inflammatory responses,milk production and milk quality in dairy cows

The objective of this study was to evaluate the effects of continuous low dose infusion of lipopolysaccharide (LPS) on inflammatory responses and milk production and quality in lactating dairy cows. Eight Holstein cows were assigned to two treatments in a cross‐over experimental design. Cows were infused intravenously either with saline solution or with saline solution containing LPS from Escherichia coli O111:B4 at a dose of 0.01 μg LPS/kg body weight for approximately 6 hr each day during a seven‐day trial. The clinical symptoms and milk production performance were observed. Milk samples were analysed for conventional components, fatty acids and amino acids. And jugular vein and mammary vein plasma samples were analysed for concentrations of cytokines and acute phase proteins. LPS infusion decreased feed intake and milk yield. An increase in body temperature was observed after LPS infusion. LPS infusion also increased plasma concentrations of interleukin‐1β, serum amyloid A, LPS‐binding protein, C‐reactive protein and haptoglobin. LPS infusion decreased the contents of some fatty acids, such as C17:1, C18:0, C18:1n9 (trans) and C18:2n6 (trans), and most amino acids except for methionine, threonine, histidine, cysteine, tyrosine and proline in the milk. The results indicated that a continued low dose infusion of LPS can induce an inflammatory response, decrease milk production and reduce milk quality.     

Determination of the intramammary dose of benzylpenicillin required to maintain an adequate concentration in the milk to inhibit Gram‐positive bacteria in the clinically normal udder for 24 hr

The aim of this study was to determine the intramammary dose of benzylpenicillin required to maintain a concentration in the milk above the MIC for the Gram‐positive bacteria that cause mastitis. The product used in this study was a commercially available procaine benzylpenicillin in an oily suspension with micronized particles. Three dose levels were used: 200,000, 300,000, and 600,000 IU. Concentrations of benzylpenicillin in cow milk and plasma were determined after a single intramammary dose was administered into one quarter of each of the five cows in each treatment group. Samples were analyzed using an HPLC‐MS/MS method, which was validated during the study. Concentrations in the milk were well above the MIC for the target pathogens for all doses tested. There was a linear dose‐dependent increase in the mean AUCs of benzylpenicillin concentrations in plasma and milk. At the first milking, 12 hr after dosing, there was a significant difference between the mean milk benzylpenicillin concentrations in cows treated with a dose of 600,000 IU, and those treated with 200,000 or 300,000 IU. Although this study shows a linear relationship between the dose of procaine benzylpenicillin administered and the concentration in the milk in the healthy udder, it would be useful to conduct studies on cows with mastitis to define the optimum dose and duration of intramammary treatment with benzylpenicillin.     

Closantel plasma and milk disposition in dairy goats: assessment of drug residues in cheese and ricotta

Closantel (CLS) is currently used in programs for the strategic control of gastrointestinal nematodes. CLS is extralabel used in different dairy goat production systems. From available data in dairy cows, it can be concluded that residues of CLS persist in milk. The current work evaluated the concentration profiles of CLS in plasma and milk from lactating orally treated dairy goats to assess the residues pattern in dairy products such as cheese and ricotta. Six (6) female Saanen dairy goats were treated orally with CLS administered at 10 mg/kg. Blood and milk samples were collected between 0 and 36 days post‐treatment. The whole milk production was collected at 1, 4, 7, and 10 days post‐treatment to produce soft cheese and ricotta. CLS concentrations in plasma, milk, cheese, whey, and ricotta were determined by HPLC. The concentrations of CLS measured in plasma were higher than those measured in milk at all sampling times. However, the calculated withdrawal time for CLS in milk was between 39 and 43 days postadministration to dairy goats. CLS residual concentrations in cheese (between 0.93 and 1.8 μg/g) were higher than those measured in the milk used for its production. CLS concentrations in ricotta were sixfold higher than those in the milk and 20‐fold higher than those in the whey used for its production. The persistent and high residual concentrations of CLS in the milk and in the cheese and ricotta should be seriously considered before issuing any recommendation on the extralabel use of CLS in dairy goat farms.     

The bioavailability and pharmacokinetics of an amoxicillin–clavulanic acid granular combination after intravenous and oral administration in swine

The pharmacokinetic behaviours of amoxicillin (AMX) and clavulanic acid (CA) in swine were studied after either an intravenous or oral administration of AMX (10 mg/kg) and CA (2.5 mg/kg). The concentrations of these two medicines in swine plasma were determined using high‐performance liquid chromatographic‐tandem mass spectrometry, and the data were analysed using a noncompartmental model with the WinNonlin software. After intravenous administration, both substances were absorbed rapidly and reached their effective therapeutic concentration quickly. CA was eliminated more slowly compared with AMX. Moreover, the distribution volume of AMX was larger than that of CA, suggesting that AMX could penetrate tissues better. After oral administration of the granular formulation, no significant difference was observed in the mean elimination half‐life value between AMX and CA. The mean maximal plasma concentrations of AMX and CA, reached after 1.14 and 1.32 hr, were 2.58 and 1.91 μg/m, respectively. The mean oral bioavailability of AMX and CA was 23.6% and 26.4%, respectively. After oral administration, the T>MIC₅₀ for three common respiratory pathogens was over 6.12 hr. Therefore, oral administration could be more effective in the clinical therapy of pigs, especially when administered twice daily.     

Pharmacokinetics of enrofloxacin after oral,intramuscular and bath administration in crucian carp (Carassius auratus gibelio)

The pharmacokinetics of enrofloxacin (ENR) was studied in crucian carp (Carassius auratus gibelio) after single administration by intramuscular (IM) injection and oral gavage (PO) at a dose of 10 mg/kg body weight and by 5 mg/L bath for 5 hr at 25°C. The plasma concentrations of ENR and ciprofloxacin (CIP) were determined by HPLC. Pharmacokinetic parameters were calculated based on mean ENR or CIP concentrations using WinNonlin 6.1 software. After IM, PO and bath administration, the maximum plasma concentration (C_max) of 2.29, 3.24 and 0.36 μg/ml was obtained at 4.08, 0.68 and 0 hr, respectively; the elimination half‐life (T_1/2β) was 80.95, 62.17 and 61.15 hr, respectively; the area under the concentration–time curve (AUC) values were 223.46, 162.72 and 14.91 μg hr/ml, respectively. CIP, an active metabolite of enrofloxacin, was detected and measured after all methods of drug administration except bath. It is possible and practical to obtain therapeutic blood concentrations of enrofloxacin in the crucian carp using IM, PO and bath immersion administration.     

Effects of vitamin E and selenium supplementation on blood lipid peroxidation and cortisol concentration in dairy cows undergoing omentopexy

Twenty dairy cows with left abomasal displacement were used to investigate the effects of vitamin E and selenium treatment on thiobarbituric acid reactive substances (TBARS) and blood cortisol in dairy cows stressed by omentopexy. The cows were randomly divided into two groups. Ten hours before surgery 6 g of DL‐α‐tocopheryl acetate (6 mg/kg) and 67 mg of natrium selenite (0.1 mg/kg) in volume of 40 ml (Vitaselen^®) were administered subcutaneously to 10 cows; the control animals (n = 10) received an equivalent volume of injectable water (40 ml). The injection of vitamin E and selenium produced a rapid rise (p < .05) in blood α‐tocopherol and selenium concentrations. The serum vitamin E increased several times 10 hr after vitamin E and Se injection and raised continuously to the highest average concentration 21.6 mg/L at hr 24 after the surgery. The highest selenium concentration was seen 10 hr after selenium administration with holding the increased concentrations in comparison with initial ones during the whole study. Two‐way ANOVA did not show significant treatment effect on plasma concentrations TBARS in the study. The plasma concentrations of thiobarbituric acid reactive substances reached the maximum value of 0.18 μmol/L in the control group 5 hr after the surgery. Twenty‐four hours after the surgery, the TBARS values returned to the initial ones. Serum cortisol increased in both groups after surgery. The highest cortisol concentrations were reached at 1 hr after surgery in the experimental and control group (56.7 ± 28.8 and 65.3 ± 26.1 μg/L respectively). A return to the levels similar to the initial ones was recognized 24 hr after the surgery. The ANOVA revealed a significant effect of vitamin E and selenium injection on plasma cortisol (p < .05). In conclusion, we have demonstrated that abdominal surgery resulted in typical stress changes with no significant effects of a single vitamin E/Se injection on blood lipid peroxidation. In addition, a weaker cortisol response to the abdominal surgery was recognized in animals treated with vitamin E and selenium.     

Effect of tannins and saponins in Samanea saman on rumen environment,milk yield and milk composition in lactating dairy cows

The objective of this study was to investigate the effects of tannins and saponins in Samanea saman on rumen fermentation, milk yield and milk composition in lactating dairy cows. Four multiparous early‐lactating dairy cows (Holstein‐Friesian cross‐bred, 75%) with an initial body weight (BW) of 405 ± 40 kg and 36 ± 8 day in milk were randomly assigned to receive dietary treatments according to a 4 × 4 Latin square design. The four dietary treatments were unsupplemented (control), supplemented with rain tree pod (S. saman) meal (RPM) at 60 g/kg, supplemented with palm oil (PO) at 20 g/kg, and supplemented with RPM at 60 g/kg and PO at 20 g/kg (RPO), of total dry matter (DM) intake. Cows were fed with concentrate diets at a ratio of concentrate to milk yield of 1:2, and chopped 30 g/kg of urea‐treated rice straw was fed ad libitum. The RPM contained condensed tannins and crude saponins at 88 and 141 g/kg of DM respectively. It was found that s upplementation with RPM and/or PO to dairy cows diets did not show negative effect on ruminal pH, blood urea nitrogen and milk urea nitrogen concentration (p > 0.05). However, supplementation with RPM resulted in lower ammonia nitrogen (NH₃‐N) concentration (p < 0.05). In addition, propionic acid and milk production increased while acetic acid, acetic to propionic ratio, methane production, methanogens and protozoal population decreased with RPM and/or PO supplementation. Furthermore, addition of PO and RPO in the diets increased milk fat while supplementation of RPM resulted in greater milk protein and Fibrobacter succinogenes numbers (p < 0.05). The population of Ruminococcus flavefaciens and Ruminococcus albus were not affected by any treatments. The findings on the present study showed that supplementation with RPM and RPO to diets of cows improved the rumen environment and increased milk yield, content of milk protein and milk fat.     

Dose dependent disposition of sulphadimidine and of its N4-acetyl and hydroxy metabolites in plasma and milk of dairy cows

The disposition of sulphadimidine (SDM) and of its N4-acetyl (N4-SDM) and two hydroxy metabolites, 6-hydroxymethyl-(SCH2OH) and 5-hydroxyasulphadimidine (SOH), was studied in plasma and milk of dairy cows following intramuscular or intravenous administration of sulphadimididine-33.3% at doses of 10, 45, 50, and 100 mg/kg. The main metabolite in plasma as well as in milk was SCH2OH. The metabolite percentages, the final plasma elimination half-lives, and the time of peak SDM concentrations in milk are presented for different dosages. The concentrations of SDM and its metabolites in milk ran parallel to those in plasma beyond 4 hours p.i. The metabolite concentrations in plasma and milk were lower than those of the parent SDM. Sulphate and glucuronide metabolites could not be detected in milk. At high doses (45 mg/kg or more) and SDM plasma concentrations exceeding 20 micrograms/ml, a capacity limited metabolism of SDM to SCH2OH was noticed, viz. a steady state concentration of SCH2OH and a biphasic elimination pattern for SDM and SCH2OH in plasma and milk. The mean ultrafiltrate ratios of the milk to plasma concentrations with respect to SDM, SCH2OH, SOH, and N4-SDM were: 0.69, 0.22, 020, and 0.63, respectively. The total amount of SDM and its metabolites recovered from the milk after milking twice daily over the whole experimental time was less than 2% of the applied dose. A bioassay method allowed of detecting qualitatively SDM concentrations exceeding 0.2 micrograms/ml in plasma or milk. Withholding times for edible tissues and milk are suggested.     

Plasma kinetics,excretion in milk of eprinomectin,and its efficacy against Hypoderma spp. following topical administration in yaks

The plasma pharmacokinetics and mammary excretion of eprinomectin were determined in dairy yaks following topical administration at a dose of 0.5 mg/kg. The kinetics of plasma and milk concentrations were analyzed using a noncompartmental model. Plasma and milk concentrations of eprinomectin increased to reach maximal concentrations of 5.45 ± 2.84 and 2.29 ± 0.90 ng/mL at a T_max of 1.79 ± 0.57 and 2.00 ± 0.82 days, respectively. The concentration of eprinomectin in plasma was remained >0.5 ng/mL for more than 30 days after administration. The mean residence times of eprinomectin in plasma and milk were 14.73 ± 6.22 and 9.37 ± 2.81 days, respectively. The AUC value in plasma (55.89 ± 18.16 ng day/mL) was threefold greater than that in milk (18.02 ± 6.48 ng day/mL). The AUC milk/plasma ratio was 0.33 ± 0.08. The systemic availability of eprinomectin in yaks was lower than that observed value in other domestic bovines. The low level of eprinomectin excretion in milk suggests that eprinomectin can be used in yaks with zero milk‐withdrawal time. The efficacy of eprinomectin against naturally acquired larvae of Hypoderma spp. was also determined in yaks. Topically administrated eprinomectin at a dose of 0.5 mg/kg was 100% efficacious against larvae of Hypoderma bovis, H. lineatum, and H. sinense.     

Pharmacokinetic profiles of amoxicillin trihydrate in freshwater crocodiles (Crocodylus siamensis) after intramuscular administration at two doses

The aim of the present study was to elucidate the pharmacokinetic profiles of amoxicillin trihydrate (AMX) in Siamese freshwater crocodiles (Crocodylus siamensis). Crocodiles were administered a single intramuscular injection of AMX, at a dose of either 5 or 10 mg/kg body weight (b.w.). Blood samples were collected at preassigned times up to 120 hr. The plasma concentrations of AMX were measured using a validated liquid chromatography tandem-mass spectrometry method. AMX plasma concentrations were quantifiable for up to 72 hr (5 mg/kg b.w.) and 96 hr (10 mg/kg b.w.). The elimination half-life (t_1/2λz) of AMX following dosing at 5 mg/kg b.w. (8.72 ± 0.61 hr) was almost identical to that following administration at 10 mg/kg b.w (8.98 ± 1.13 hr). The maximum concentration and area under the curve from zero to the last values of AMX increased in a dose-dependent fashion. The average binding percentage of AMX to plasma protein was 21.24%. Based on the pharmacokinetic data, susceptibility break point, and the surrogate PK-PD index (T > MIC, 0.25 μg/ml), intramuscular administration of AMX at dose of 5 mg/kg b.w. every 4 days might be appropriate for the treatment of susceptible bacterial infections in freshwater crocodiles.     

Pharmacokinetics of cefquinome in crucian carp (Carassius auratus gibelio) after oral,intramuscular, intraperitoneal,and bath administration

The pharmacokinetics (PK) of cefquinome (CEQ) was studied in crucian carp (Carassius auratus gibelio) after single oral, intramuscular (i.m.), and intraperitoneal (i.p.) administration at a dose of 10 mg/kg body weight and following incubation in a 5 mg/L bath for 5 hr at 25°C. The plasma concentration of CEQ was determined using high‐performance liquid chromatography (HPLC). PK parameters were calculated based on mean CEQ concentration using WinNonlin 6.1 software. The disposition of CEQ following oral, i.m., or i.p. administration was best described by a two‐compartment open model with first‐order absorption. After oral, i.m., and i.p. administration, the maximum plasma concentration (C_max) values were 1.52, 40.53, and 67.87 μg/ml obtained at 0.25, 0.23, and 0.35 hr, respectively, while the elimination half‐life (T_1/2β) values were 4.68, 7.39, and 6.88 hr, respectively; the area under the concentration–time curve (AUC) values were 8.61, 339.11, and 495.06 μg hr/ml, respectively. No CEQ was detected in the plasma after bath incubation. Therapeutic blood concentrations of CEQ can be achieved in the crucian carp following i.m. and i.p. administration at a dosage of 10 mg/kg once every 2 days.     

Effects of genetic capacity on milk production and on plasma metabolites in dairy cows during post-ruminal or intravenous carbohydrates or amino acid infusions

The objectives of this study were to investigate the effects of genetic capacity on abomasal and intravenous infusions of wheat starch or glucose (CHO) or a mixture of amino acids (AA) on milk production, nitrogen utilization efficiency, plasma metabolites and hormones of dairy cows in early and late lactation. Eight cows from two genetic lines selected for low (L) and high (H) milk production were used in a 4 × 4 Latin square design. The mean differences in pedigree index between the two groups were 1639 kg milk and 55 kg protein yield based on 305 days lactation. Infusions were: 1) starch in the abomasum (SP), 2) glucose in the blood (GB), 3) AA in the abomasum (AP), and 4) AA in the blood (AB). The experiment was conducted in early lactation (start: 57 ± 4 and 52 ± 2 days postpartum, 31.3 ± 2.8 and 34.7 ± 1.4 kg milk for L and H cows, respectively) and repeated with the same animals and treatments in late lactation (start: 168 ± 4 and 163 ± 2 d postpartum, 21.0 ± 1.9 and 23.8 ± 0.7 kg milk for L and H cows, respectively). Daily amounts infused were on average 354 and 258 g in early and late lactation, respectively. The cows were restrictively fed a basal diet consisting of concentrate mixture and grass silage (55:45 on DM basis). Differences in milk yield and ECM between the genetic groups were 3.7 and 3.3 kg in early lactation and 2.9 and 2.0 kg in late lactation, respectively, but the difference was not significant (P > 0.10). Minor effects of genetic group were found in milk production and plasma metabolite concentrations. However, the extraction rates of EAA, BCAA, NEAA and TAA were higher (P < 0.05) in H cows than in L cows in early lactation but not in late lactation. OM and CP digestibility and hormones were affected by genetic group or genetic group × treatment interaction. It is concluded that genetic capacity is important for digestion and metabolism of nutrients, and particularly, how hormone levels are influenced by different nutrient supply.     

Pharmacokinetics of tigecycline in turkeys following different routes of administration

The aim of this research had been to determine the pharmacokinetics of tigecycline (TIG) in turkey after intravenous (i.v.), intramuscular (i.m.), subcutaneous (s.c.), and oral (p.o.) administration at a dose of 10 mg/kg. TIG concentrations in plasma were determined using high‐performance liquid chromatography with tandem mass spectrometry. Mean concentrations of TIG in turkey plasma in the i.v. group were significantly higher than concentrations of this drug obtained after using the other administration routes. No significant differences were demonstrated in respect to the concentrations achieved after i.m. and s.c. administration. The bioavailability of TIG after i.m., s.c., and p.o. administration was 32.59 ± 5.99%, 34.91 ± 9.62%, and 0.97 ± 0.57%, respectively. Values of half‐life in the elimination phase were 23.49 ± 6.51 hr, 25.42 ± 4.42 hr, and 26.62 ± 5.19 hr in i.v., i.m., and s.c. groups, respectively, values of mean residence time were 7.92 ± 1.41 hr, 19.62 ± 2.82 hr, and 17.55 ± 2.59 hr in i.v., i.m., and s.c. groups, respectively, whereas the volume of distribution was 14.85 ± 5.71 L/kg, 14.68 ± 2.56 L/kg, and 15.37 ± 3.00 L/kg in i.v., i.m., and s.c. groups, respectively. Because TIG is not absorbed from the gastrointestinal tract in turkeys to a clinically significant degree, this drug given p.o. could find application in commercial turkey farms only to treat gastrointestinal tract infections.     

Pharmacokinetics of midazolam and its major metabolite 1‐hydroxymidazolam in the ball python (Python regius) after intracardiac and intramuscular administrations

Midazolam is a benzodiazepine with sedative, muscle relaxant, anxiolytic, and anticonvulsant effects. Twelve ball pythons (Python regius) were used in a parallel study evaluating the pharmacokinetics of 1 mg/kg midazolam following a single intracardiac (IC) or intramuscular (IM) administration. Blood was collected from a central venous catheter placed 7 days prior, or by cardiocentesis, at 15 time points starting just prior to and up to 72 hr after drug administration. Plasma concentrations of midazolam and 1‐hydroxymidazolam were determined by the use of high‐performance liquid chromatography tandem‐mass spectrometry and pharmacokinetic parameters were estimated using noncompartmental analysis. The mean ± SD terminal half‐lives of IC and IM midazolam were 12.04 ± 3.25 hr and 16.54 ± 7.10 hr, respectively. The area under the concentration‐time curve extrapolated to infinity, clearance, and apparent volume of distribution in steady‐state of IC midazolam were 19,112.3 ± 3,095.9 ng*hr/ml, 0.053 ± 0.008 L hr^?1 kg^?1, and 0.865 ± 0.289 L/kg, respectively. The bioavailability of IM midazolam was estimated at 89%. Maximum plasma concentrations following an IM administration were reached 2.33 ± 0.98 hr and 24.00 ± 14.12 hr postinjection for midazolam and 1‐hydroxymidazolam, respectively, and 22.33 ± 20.26 hr postinjection for 1‐hydroxymidazolam following IC administration.     

Effects of clinical mastitis on reproductive and milk performance of Holstein cows in Morocco

The aim of this study was to determine the influence of clinical mastitis and time of first mastitis occurrence on reproductive and milk performance of Holstein cows. Data were collected in a dairy farm from 2008 to 2012 on 1725 cows, among which 464 cows with mastitis. To determine the influence of clinical mastitis on reproductive and milk performance, models included fixed effects of parity, calving season, calving year, and group (cows with and with no mastitis). To determine the effect of time of 1st mastitis occurrence on reproductive performance, the mastitic cows group was further reclassified into three groups: prior to 60 days, between 60 and 90 days and greater than 90 days postpartum. For milk performance, the mastitic cows group was divided into two groups: before and after peak milk yield. Clinical mastitis had significant effects on calving to first AI interval, milk yield, and fat yield, but a non-significant effect on days open, number of inseminations per conception, and milk fat percentage. Mastitic cows had a calving to first AI interval 6.1 days longer and 549.6 kg milk and 20.4 kg fat per 305 days of lactation lower than those with no mastitis. Time of 1st mastitis occurrence did not have any significant effect on reproductive performance. Further, milk and fat yields of cows diseased before peak milk yield were 506 kg and 23.9 kg, respectively, lower than those of cows affected after peak milk yield. Extra attention needs to be paid to mastitis during the early postpartum period.