Effect of preoperative administration of erythromycin or flunixin meglumine on postoperative abomasal emptying rate in dairy cows undergoing surgical correction of left displacement of the abomasum

Objective: To determine whether preoperative administration of erythromycin or flunixin meglumine altered postoperative abomasal emptying rate, rumen contraction rate, or milk production in dairy cattle undergoing surgical correction of left displacement of the abomasum (LDA). DESIGN: Nonrandomized, controlled clinical trial. ANIMALS: 45 lactating Holstein-Friesian cows with LDA. PROCEDURES: Cows were alternately assigned to an erythromycin (10 mg/kg [4.5 mg/lb], IM), flunixin (2.2 mg/kg [1.0 mg/lb], IV), or control group (n = 15/group). Treatments were administered once 1 hour before surgical correction of LDA. D-Xylose solution (50%; 0.5 g/kg [0.23 g/lb]) was injected into the abomasal lumen during surgery, and venous blood samples were periodically obtained to determine time to maximum serum D-xylose concentration. RESULTS: Abomasal emptying rate was significantly faster in cows treated with erythromycin (mean +/- SD time to maximum serum D-xylose concentration, 149 +/- 48 minutes) than in control cows (277 +/- 95 minutes) but was not significantly different between cows treated with flunixin (230 +/- 49 minutes) and control cows. Cows treated with erythromycin had significantly greater milk production, relative to production before surgery, on postoperative days 1 and 2 than did control cows. Cows in the erythromycin and flunixin groups had a significantly higher rumen contraction rate on the first postoperative day than did control cows. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that preoperative administration of a single dose of erythromycin increased abomasal emptying rate, rumen contraction rate, and milk production in the immediate postoperative period in cows undergoing surgical correction of LDA.     

Assessment of the effects of erythromycin, neostigmine, and metoclopramide on abomasal motility and emptying rate in calves

OBJECTIVE: To determine and compare the effects of erythromycin, neostigmine, and metoclopramide on abomasal motility and emptying rate in suckling calves. ANIMALS: 6 male Holstein calves (15 to 40 days of age). PROCEDURE: Calves were monitored for 1 hour before being fed milk replacer (60 mL/kg; time, 0 minutes) and then were monitored for another 3 hours. Calves received 6 treatments in randomized order: erythromycin (8.8 mg/kg, IM) at -30 minutes; low-dose erythromycin (0.88 mg/kg, IM) at -30 minutes; erythromycin (8.8 mg/kg, IM) at -30 minutes and neostigmine (0.02 mg/kg, SC) at -30 and 90 minutes; neostigmine (0.02 mg/kg, SC) at -30 and 90 minutes; metoclopramide (0.1 mg/kg, IM) at-30 and 90 minutes; and placebo (2 mL of saline [0.9% NaCl] solution, SC) at -30 minutes. Abomasal volume was calculated from ultrasonographic measurements of abomasal width, length, and height. Abomasal motility and emptying rate were assessed by measuring luminal pressure and change in abomasal volume over time. RESULTS: Administration of erythromycin (8.8 mg/kg) increased the frequency of abomasal luminal pressure waves and the mean abomasal luminal pressure and decreased the half-time of abomasal emptying by 37%. Administration of metoclopramide, neostigmine, and low-dose erythromycin (0.88 mg/kg) did not alter abomasal motility, mean luminal pressure, or emptying rate. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that administration of erythromycin at the labeled antimicrobial dose (8.8 mg/kg, IM) exerted an immediate, marked prokinetic effect in healthy suckling calves, whereas administration of metoclopramide or neostigmine did not alter abomasal motility or emptying rate.     

Serum Amyloid A and Haptoglobin Concentrations and Liver Fat Percentage in Lactating Dairy Cows with Abomasal Displacement

Background: There has been increased interest in measuring the serum concentration of acute phase reactants such as serum amyloid A [SAA] and haptoglobin [haptoglobin] in periparturient cattle in order to provide a method for detecting the presence of inflammation or bacterial infection.
Objectives: To determine whether [SAA] and [haptoglobin] are increased in cows with displaced abomasum as compared with healthy dairy cows.
Animals: Fifty-four adult dairy cows in early lactation that had left displaced abomasum (LDA, n = 34), right displaced abomasum or abomasal volvulus (RDA/AV, n = 11), or were healthy on physical examination (control, n = 9).
Materials and Methods: Inflammatory diseases or bacterial infections such as mastitis, metritis, or pneumonia were not clinically apparent in any animal. Jugular venous blood was obtained from all cows and analyzed. Liver samples were obtained by biopsy in cattle with abomasal displacement.
Results: [SAA] and [haptoglobin] concentrations were increased in cows with LDA or RDA/AV as compared with healthy controls. Cows with displaced abomasum had mild to moderate hepatic lipidosis, based on liver fat percentages of 9.3 ± 5.3% (mean ± SD, LDA) and 10.8 ± 7.7% (RDA/AV). [SAA] and [haptoglobin] were most strongly associated with liver fat percentage, r _s=+0.55 ( P < .0001) and r _s=+0.42 ( P = .0041), respectively.
Conclusions and Clinical Importance: An increase in [SAA] or [haptoglobin] in postparturient dairy cows with LDA or RDA/AV is not specific for inflammation or bacterial infection. An increase in [SAA] or [haptoglobin] may indicate the presence of hepatic lipidosis in cattle with abomasal displacement.     

Effect of erythromycin and gentamicin on abomasal emptying rate in suckling calves

BACKGROUND: Commonly used dosage protocols for antimicrobial agents may alter the rate of gastric emptying. HYPOTHESIS: Parenteral administration of erythromycin increases and gentamicin decreases the rate of abomasal emptying. ANIMALS: Five male Holstein-Friesian calves (8-15 days of age). METHODS: Calves received each of the following 4 IM treatments in random order: control, 2 mL of 0.9% NaCl; erythromycin, 8.8 mg/kg; low-dose gentamicin, 4.4 mg/kg; high-dose gentamicin, 6.6 mg/kg. Abomasal emptying rate was assessed by acetaminophen and glucose absorption. Calves were fed 2 L of cow's milk containing acetaminophen (50 mg/kg body weight) 30 minutes after each treatment was administered, and jugular venous blood samples were obtained periodically after suckling. The maximum observed plasma acetaminophen concentration (actual C(max)) and time of actual C(max) (actual T(max)) were determined, and pharmacokinetic modeling was used to calculate model C(max) and model T(max). RESULTS: Erythromycin increased abomasal emptying rate, as indicated by a shorter time to actual T(max) and model T(max) (P < .05). Abomasal emptying rate after injection of low-dose gentamicin was similar to that of control. Administration of high-dose gentamicin resulted in a longer time to actual T(max) (P= .021) but did not change model T(max) (P= .62). CONCLUSIONS AND CLINICAL RELEVANCE: IM injection of erythromycin increased abomasal emptying rate in dairy calves, whereas low-dose and high-dose gentamicin did not alter the rate of abomasal emptying as measured by acetaminophen kinetics and glucose absorption. The clinical relevance of these findings remains to be determined.     

Effect of parenteral administration of erythromycin, tilmicosin, and tylosin on abomasal emptying rate in suckling calves

OBJECTIVE: To determine the effect of parenteral administration of erythromycin, tilmicosin, and tylosin on abomasal emptying rate in suckling calves. ANIMALS: 8 male Holstein-Friesian calves < 35 days old. PROCEDURES: Calves received each of 4 treatments in random order (2 mL of saline [0.9% NaCl] solution, IM [control treatment]; erythromycin, 8.8 mg/kg, IM; tilmicosin, 10 mg/kg, SC; and tylosin, 17.6 mg/kg, IM). Calves were fed 2 L of milk replacer containing acetaminophen (50 mg/kg) 30 minutes later. Jugular venous blood samples and transabdominal ultrasonographic abomasal dimensions were obtained periodically after suckling. Abomasal emptying rate was assessed on the basis of the time to maximal plasma acetaminophen concentration and ultrasonographic determination of the halftime of abomasal emptying. One-tailed Dunnett post tests were conducted whenever the F value for group was significant. RESULTS: Emptying rate was faster for erythromycin, tilimicosin, and tylosin than for the control treatment, as determined on the basis of time to maximal plasma acetaminophen concentration. Ultrasonography indicated that the half-time of abomasal emptying was significantly shorter for erythromycin than for the control treatment. Tylosin and tilmicosin accelerated the abomasal emptying rate, but not significantly, relative to the emptying rate for the control treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of erythromycin, tilmicosin, and tylosin at the label dosage increased abomasal emptying rate in calves. The clinical importance of an increase in abomasal emptying rate in cattle remains to be determined.     

Effect of spiramycin and tulathromycin on abomasal emptying rate in milk-fed calves

Impaired abomasal motility is common in cattle with abomasal disorders. The macrolide erythromycin has been demonstrated to be an effective prokinetic agent in healthy calves and in adult cattle with abomasal volvulus or left displaced abomasum. We hypothesized that 2 structurally related macrolides, spiramycin and tulathromycin, would also be effective prokinetic agents in cattle. Six milk-fed, male, Holstein-Friesian calves were administered each of the following 4 treatments: spiramycin, 75 000 IU/kg BW, IM, this dose approximates 25 mg/kg BW, IM; tulathromycin, 2.5 mg/kg BW, SC; 2 mL of 0.9% NaCl (negative control); and erythromycin, 8.8 mg/kg BW, IM (positive control). Calves were fed 2 L of cow’s milk containing acetaminophen (50 mg/kg body weight) 30 min after each treatment was administered and jugular venous blood samples were obtained periodically after the start of sucking. Abomasal emptying rate was assessed by the time to maximal plasma acetaminophen concentration. Spiramycin, tulathromycin, and the positive control erythromycin increased abomasal emptying rate compared to the negative control. We conclude that the labeled antimicrobial dose of spiramycin and tulathromycin increases the abomasal emptying rate in healthy milk-fed calves. Additional studies investigating whether spiramycin and tulathromycin exert a prokinetic effect in adult cattle with abomasal hypomotility appear indicated.     

Bioavailability and pharmacokinetics of metoclopramide in cattle

The bioavailability of metoclopramide was investigated in three steers following administration of 8 mg/kg by the oral, abomasal (cannula), and intravenous routes, using a Latin square design. The mean (± SD) oral and abomasal bioavailabilitles were 51.3 ± 30.7% and 76.2 ± 15.5%, respectively. The mean value for clearance ( C1 ) was 20.1 ± 5.9 ml/min and the volume of distribution ( V _d) was 0.51 ± 0.19 1/kg. Additionalpharmacokmetic parameters for metoclopramide were determined following intravenous administration to seven cows. A predominate two-compartment model of distribution was found in six cows with a t _1/2α harmonic mean of 24.2 min and a range of 11.2–72.4 min, a t _1/2β harmonic mean of 53.1 min and a range of 31.1–134.1 min, a Cl of 42.2 ± 8.7 ml/min, and a V _d of 2.1 ± 0.8 1/kg. To better define the relationship between metoclopramide concentration and release of prolactin, a treatment-by-subjects infusion study was conducted in which four different loading doses followed by constant infusion were used. A steady-state metoclopramide concentration ( MCP _ss) of 8.8 ± 2.6 ng/ml was associated with a three-fold elevation of prolactin to a mean value of 12.1 ± 3.1 ng/ml in six yearling steers. Steady state serum prolactin concentrations ( PRL _ss) did not rise significantly above 23.3 ± 6.9 ng/ml, even when MCP _ss reached a concentration of 518.5 ±151.2 ng/ml. The short half-life, moderate V _d, low minimum pharmacologically effective concentration, and rapid C1 found for metoclopramide in cattle in this study, suggest that a continuous release device could potentially be useful in the application of this drug in the prevention and treatment of fescue toxicosis.     

Use of the D-xylose absorption test to measure abomasal emptying rate in healthy lactating Holstein-Friesian cows and in cows with left displaced abomasum or abomasal volvulus

We determined the abomasal emptying rates of Holstein-Friesian cows at different stages of lactation, with left displaced abomasum (LDA), or immediately after surgical correction of LDA or abomasal volvulus (AV). D-xylose (0.5 g/kg body weight [BW], 50% solution) was injected into the abomasum in healthy cows (group 1, 4-7 days in milk [DIM], n = 7; group 2, 90-120 DIM, n = 7; group 3, > 300 DIM, n = 7) and in cows with LDA (n = 10; group 4). D-xylose was injected into the abomasum during right flank laparotomy in cows with LDA (n = 22; group 5) and cows with AV (n = 15; group 6). The time to maximal serum D-xylose concentration was used as an index of emptying rate. The abomasal emptying rates for cows in groups 1, 2, and 3 were similar, whereas emptying was slower in cows with LDA and in cows after surgical correction of LDA or AV. The abomasal emptying rate of cows with LDA was slowed to a greater extent immediately after surgery, when compared to the rate obtained before surgery. There was no difference in abomasal emptying rate immediately after surgical correction between cows with LDA or AV. The results indicate that the increased incidence of LDA in the first month of lactation is not associated with an intrinsic decrease in abomasal emptying rate in healthy cows. Our findings also demonstrate that surgical correction further slows the emptying rate in cows with LDA.     

Effect of acepromazine or xylazine on tear production as measured by Schirmer tear test in normal cats

Objective  To evaluate the effect of acepromazine or xylazine on Schirmer tear test 1 results in clinically normal cats.
Animals  Sixteen healthy cross-breed cats.
Procedure  The animals were randomly divided into two groups of eight cats each. The first group was sedated with acepromazine alone (0.2 mg/kg) and the second group received only xylazine (2 mg/kg). All cats had Schirmer tear test (STT) readings taken prior to sedation and at 15 and 25 min postsedation.
Results  Sedation with acepromazine or xylazine in cats with normal pre-sedation STT 1 values caused a statistically significant decrease in mean values of tear production in both groups. In acepromazine group the mean ± SEM STT at T₁₅ and T₂₅ were 4.31 ± 0.98 ( P  < 0.001) and 5.18 ± 1.07 ( P  = 0.002). The post-treatment mean ± SEM values in xylazine group were 2.18 ± 0.97 ( P  < 0.001) and 2.62 ± 1.17 ( P  = 0.001) at 15 and 25 min respectively. Comparison between T₁₅ and T₂₅ in acepromazine group ( P  = 0.49) and xylazine group ( P  = 0.56) revealed no significant differences.
Conclusion  These observations indicate that both acepromazine or xylazine significantly reduced tear production in clinically normal cats. In cats, clinicians should measure STT values prior to utilizing acepromazine or xylazine as sedatives in order to accurately assess the results. Moreover, sterile ocular lubricant or tear replacement should be used as a corneal protectant during sedation with these drugs.     

Intramuscular, intravenous and oral levetiracetam in dogs: safety and pharmacokinetics

Intravenous (IV) levetiracetam (LEV) is available for humans for bridge therapy when the oral route is unavailable. We investigated the safety and pharmacokinetics of LEV administered intramuscularly (IM), IV, and orally to dogs.
Six Hound dogs received 19.5–22.6 mg/kg of LEV IM, IV and orally with a wash-out period in between. All dogs received 500 mg LEV orally and 5 mL of 100 mg/mL LEV IM. Three dogs received 500 mg of LEV IV and three dogs received 250 mg LEV IV with 250 mg given perivascularly to approximate extravasation. Safety was assessed using a pain scale at time of IM administration and histopathological examination 24 h to 5 days after injection.
Intravenous LEV half-life was 180 ± 18 min. Bioavailability of IM LEV was 100%. Mean time to T_max after IM was 40 ± 16 min. The mean C_max IM was 30.3 ± 3 μg/mL compared to the C₀ of 37 ± 5 μg/mL for IV. Mean inflammation score (0–4 scale) for IM LEV was 0.28 and for saline 0.62. Extravasation did not cause tissue damage.
Parenteral LEV is well tolerated and appears safe following IM and IV injections in dogs. Parenteral LEV should be evaluated for use in dogs with epilepsy.     

Comparison of abomasal luminal gas pressure and volume and perfusion of the abomasum in dairy cows with left displaced abomasum or abomasal volvulus

OBJECTIVE: To compare abomasal luminal gas pressure and volume and perfusion of the abomasum in dairy cows with a left displaced abomasum (LDA) or abomasal volvulus (AV). ANIMALS: 40 lactating dairy cows (25 with an LDA and 15 with an AV). PROCEDURE: Abomasal luminal gas pressure and volume and pulse oximetry values for the caudal portion of the dorsal ruminal sac and abomasal wall were measured during laparotomy. Abomasal perfusion was assessed on the basis of abomasal O2 saturation (pulse oximetry) before correction of the LDA or AV. Abomasal perfusion was also assessed after correction of the LDA or AV by measuring venous O2 saturation in the right gastroepiploic vein and calculating the abomasal oxygen-extraction ratio. RESULTS: Abomasal luminal gas pressure and volume were higher in cattle with an AV than in cattle with an LDA. Abomasal O2 saturation was lower and abomasal oxygen-extraction ratio higher in cattle with an AV, compared with values in cattle with an LDA. In cows with an AV, lactate concentration in the gastroepiploic vein was greater than that in a jugular vein, whereas no difference in lactate concentrations was detected in cows with an LDA. Abomasal luminal gas pressure was positively correlated (r, 0.51) with plasma lactate concentration in the gastroepiploic vein and negatively correlated (r, -0.32) with abomasal O2 saturation determined by use of pulse oximetry. CONCLUSIONS AND CLINICAL RELEVANCE: Abomasal perfusion decreases as luminal pressure increases in cattle with an AV or LDA.     

Pharmacokinetics of a single bolus intravenous, intramuscular and subcutaneous dose of disodium fosfomycin in horses

Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (C_S0) was 112.21 ± 1.27 μg/mL and 201.43 ± 1.56 μg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC₉₀) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 ± 2.26 μg/mL with 10 mg/kg SC and 72.14 ± 3.04 μg/mL with 20 mg/kg SC) and that fosfomycin is considered a time-dependant antimicrobial, it can be concluded that clinically effective plasma concentrations might be obtained for up to 10 h administering 20 mg/kg SC. An additional predictor of efficacy for this latter dose and route, and considering a 12 h dosing interval, could be area under the curve AUC_0-12/MIC₉₀ ratio which in this case was calculated as 996 for the 10 mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If a more resistant strain is considered, the AUC_0-12/MIC₉₀ ratio was calculated as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose.     

Abomasal size and emptying time in healthy lambs and in lambs affected by watery mouth

Contrast radiography (barium sulphate suspension fed by stomach tube) was used to assess abomasal profile area (a reflection of tone in the abomasal wall) and the rate of abomasal emptying in healthy lambs aged four to 144 hours and in lambs affected by watery mouth. In healthy lambs abomasal profile area increased from 15.1 +/- 0.56 cm2/kg at four hours of age to 23.1 +/- 1.07 cm2/kg at 24 to 48 hours (P less than 0.001). There was no change up to 48 to 72 hours but after this age there was a substantial decrease to 12.8 +/- 0.76 cm2/kg at 120 to 144 hours (P less than 0.001). The rate of abomasal emptying decreased as abomasal profile area increased. Complete emptying of the abomasum was observed within three hours of feeding in the majority of lambs aged four hours (seven out of eight) and 120 to 144 hours (13 out of 16) but only in a minority of lambs aged 24 to 48 hours (one out of 11). In lambs affected by watery mouth (mean age [+/- se] 33 +/- 2.8 hours, n = 34) abomasal profile area was greater and the rate of abomasal emptying was slower than in healthy lambs aged 24 to 48 hours. These findings confirm the previous suspicion that watery mouth is associated with an impairment of gut motility. Abomasal emptying time was prolonged in lambs aged four hours when either ewe or cow colostrum was included with the contrast medium. A similar effect was observed in lambs aged 24 to 48 hours when cow colostrum was included. The castration of lambs aged four hours with rubber rings immediately before the administration of contrast medium had no effect on the rate of abomasal emptying.     

A comparison of the various routes of administration of erythromycin in cattle

A comparison of i.v., i.m. and s.c. administration erythromycin base in polyethylene glycol at 15 mg/kg and 30 mg/kg body weight was carried out in beef-type calves of approximately 200 kg body weight. Additional evaluations were carried out with oral administration of erythromycin phosphate and erythromycin stearate. Absorption of erythromycin was very slow by both the i.m. and s.c. routes of administration with a K_ab of 0.0135 min^-1 and 0.0185 min^-1 for i.m. and 0.0032 min^-1 and 0.0074 min^-1 for s.c. at 15 mg/kg and 30 mg/kg, respectively. The bioavailability (32–42%) and peak serum concentrations were much lower with s.c. than with i.m. (60–65%) administration. The disposition of erythromycin administered i.v. appeared to be representative of dose-dependent kinetics rather than dose-independent first-order kinetics inasmuch as the elimination half-time ( t _1/2B) increased from 174.5 ± 13 min for the 15 mg/kg dosage to 239 ± 10.8 min with 30 mg/kg dosage. An acute apparent cardiovascular effect accompanied i.v. administration of erythromycin at 30 mg/kg dosage but not at 15 mg/kg. Severe diarrhea followed oral administration of either erythromycin phosphate or erythromycin stearate.     

Comparison of Naturally Occurring Proximal Duodenal Obstruction and Abomasal Volvulus in Dairy Cattle

Physical and clinicopathologic findings from six cows with proximal duodenal obstruction (PDO) and 58 cows with abomasal volvulus (AV) were compared retrospectively. Many of the physical signs were similar in cows with PDO and cows with AV, but the two conditions differed in the type of abdominal distention, and in the findings from rectal examination and abdominal auscultation. Cows with PDO had significantly lower mean values for serum sodium (Na+) and chloride ion (Cl-), and higher mean values for plasma bicarbonate [HCO3-], base excess, carbon dioxide pressure (pCO2), serum phosphate, urea nitrogen, and total protein than AV affected cattle. Cows with PDO showed hyperglycemia (range, 263-990 mg/dl; mean, 618 mg/dl) of unexplained etiology that was significantly higher than blood-glucose concentrations in AV cows (mean, 178 mg/dl). Although all AV cows with anion gap values greater than 32 mEq/l died;PDO cows with equally elevated anion gap survived. The anion gap elevations in PDO and AV cows resulted from accumulation of different anions. Although the site of obstruction of aborad flow of ingesta is similar in both disease conditions, the differences in physical and clinicopathologic findings appear to reflect differences in the degree of reticulo-omasal orifice obstruction and the degree of abomasal vascular compromise.     

Pharmacokinetics of indomethacin in sheep after intravenous and intramuscular administration

The pharmacokinetics of indomethacin (1mg/kg) was determined in six adult sheep after intravenous (i.v.) and intramuscular (i.m.) injection. Plasma concentrations were maintained within the therapeutic range (0.3–3.0 μg/mL) from 5 to 50 min after i.v. and from 5 to 60–90 min after i.m. administration. After two trials, indomethacin best fitted an open two-compartment model. The mean (±SD) volumes of distribution at steady state ( V d_ss) were 4.10 ± 1.40 and 4.21 ± 1.93 L/kg and the mean clearance values ( C l_B) were 0.17 ± 0.06 and 0.22 ± 0.12 L/h.kg for i.v. and i.m. routes, respectively. The elimination phase half-lives did not show any significant difference between routes of injection ( t _½β = 17.4 ± 4.6 and 21.25 ± 4.44 h, i.v. and i.m. respectively). After i.m. administration, plasma maximum concentration ( C _max =  1.10 ± 0.68 μg/mL) was reached 10 min after dosing; the absorption phase was fast ( K _ab = 26 ± 18 h-1) and short ( t _½ab = 2.33 ± 1.51 min) and the mean bioavailability was 91.0 ± 32.8%, although there was considerable interanimal variation. In some individuals, bioavailability was higher than 100%. This fact combined with the slower elimination phase after i.m. than after i.v. administration, could be related with enterohepatic recycling.     

Pharmacokinetics of phenylbutazone in plasma and milk of lactating dairy cows

Phenylbutazone was administered intravenously (i.v.) to a group of four lactating cows at a dosage of 6 mg/kg body weight. Whole plasma, protein-free plasma and milk were analysed for phenylbutazone residues. Pharmacokinetic parameters of total and free phenylbutazone in plasma were calculated using a non compartmental method. In regards to whole plasma data, the mean volume of distribution at steady state ( V _ss), was 147 mL/kg body weight, with a mean (± SEM) terminal elimination half-life ( t _1/2) of 40 ± 6 h. The mean clearance ( Cl ) was 3 mL/h/kg body weight. The V _ss as determined from the protein-free plasma fraction was 50 021 mL/kg body weight. This larger V _ss of free phenylbutazone compared to total plasma phenylbutazone was attributed to a high degree of plasma protein binding, as well as the greater penetration of free phenylbutazone into tissues. The mean t _1/2 of free phenylbutazone was 39 ± 5 h. This similarity to the t _1/2 estimated from total plasma phenylbutazone data is attributed to an equilibrium between free and plasma phenylbutazone during the terminal elimination phase. Mean t _1/2 as determined from milk, applying a urinary excretion rate model, was 47 ± 4 h. Milk clearance of phenylbutazone was 0.009 mL/h/kg body weight, or about 0.34% of total body clearance. Furthermore, evidence suggests that phenylbutazone either binds to milk proteins, or is actively transported into milk, as its concentration in milk was greater than that predicted due to a simple partitioning from plasma into milk.     

Abomasal fistulas in dairy cows

Abomasal fistulas were corrected surgically in 9 adult Holstein cows. Six cows had a history of right paramedian abomasopexy (RPA), and 2 cows had had a percutaneous abomasopexy using the blind-stitch technique (BSA). Fistulas developed from 2 weeks to 12 months after the RPA or BSA. In 1 cow, history was not available beyond 2 years, and no surgery had been performed in that time. All fistulas were in the right paramedian area and were draining blood and/or ingesta from necrotic abomasal tissue (8 cows) or ruminal tissue (1 cow). Surgery was performed immediately in cows with consistent hemorrhage from the fistulated tissue (4 cows). Surgery was delayed to reduce rumen contents if bleeding was absent or considered negligible (4 cows) or to stabilize the patient (1 cow). General anesthesia was used in 7 cows, local anesthesia in 2 cows. Outcome following the fistula resection was successful in the 7 cows discharged from the clinic. The occurrence of abomasal fistulation is probably related to nonabsorbable sutures penetrating the abomasal lumen during the abomasopexy procedure resulting in infection of the incision or body wall.     

Pharmacokinetics of cefoperazone in horses

The pharmacokinetics and bioavailabilty of cefoperazone (CPZ) were studied following intravenous (IV) and intramuscular (IM) administration of single doses (30 mg/kg) to horses. Concentrations in serum, urine and synovial fluid samples were measured following IV administration. CPZ concentrations in serum, synovial fluid and spongy bone samples were measured following IM administration. After IV administration a rapid distribution phase ( t _1/2(α):4.22 ± 2.73 min) was followed by a slower elimination phase ( t 1/2(β) 0.77 ± 0.19 h). The apparent volume of distribution was 0.68 ± 0.10 L/kg. Mean synovial fluid peak concentration was 5.76 ± 0.74 μg/mL. After IM administration a bioavailability of 42.00±5.33% was obtained. Half-life of absorption was 2.51 ± 0.72 min and t _1/2(β) was 1.52±0.15 h. The mean synovial fluid and spongy bone peak concentrations at 2 h after IM administration were 2.91±0.85 μg/mL and 5.56±0.70 μg/mL, respectively.     

Pharmacokinetics of kanamycin in dogs

The pharmacokinetics of kanamycin were studied in beagle dogs. A parenteral preparation of kanamycin sulphate (5% aqueous solution), which was given at a dosage level of 10 mg/kg of body weight, was the drug product used. The disposition curve which resulted from the intravenous administration of a single bolus dose of the drug was completely described by the biexponential equation:
C _p= 50e^{-0.1977 t} + 36.3e^{-0.0128 t} where C _p represents concentration of the drug in the serum at time t (in minutes) and the experimental constants are mean values. Pseudo-distribution equilibrium was rapidly attained and the apparent volumes of the central and peripheral compartments of the two-compartment open model were the same ( ca 125 ml/kg). Body clearance (mean ± S.D., n = 6) of kanamycin was 3.21 ±0.72 ml/kg/min. The half-life of the drug was short (58.18 ± 18.43 min) and independent of the route of parenteral (intravenous and intramuscular) administration. Absorption of kanamycin from the intramuscular site was rapid, with a half-time of 9.08 ± 1.10 min. A systemic availability of 89.1 ± 15.8% was obtained. Based on the bioavailability and disposition kinetics a dosage regimen consisting of the intramuscular injection of the dose (10 mg/kg) at 6 h intervals is proposed. An intravenous infusion rate of 48 μg/kgymin is predicted to establish a steady state serum concentration of 15 μg/ml, which is a therapeutic level of the antibiotic for susceptible micro-organisms.