Comparison of plasma histamine levels after intravenous administration of hydromorphone and morphine in dogs

This study compared plasma histamine concentrations, behavioral and cardiovascular parameters following intravenous administration of hydromorphone and morphine in conscious dogs. Five adult female dogs received a 15-sec bolus injection of saline, hydromorphone (0.1 and 0.2 mg/kg) or morphine (0.5 and 1.0 mg/kg) randomly at weekly intervals. Blood samples were collected from the jugular vein before and at 1, 2, 5, 15, 30, 60 and 120 min after drug administration. Plasma histamine concentration, noninvasive oscillometric blood pressure, heart rate and rhythm were evaluated. Data were analyzed with repeated measures anova and Tukey-Kramer post hoc test with a 5% significance level. Median plasma histamine increased significantly only after the higher dose of morphine. Maximum plasma histamine measured was 0.8 ng/mL after saline and, after the lower and higher doses, respectively, 10.2 and 9.7 ng/mL for hydromorphone, and 440 and 589 ng/mL for morphine. One dog became hypotensive immediately after receiving the highest dose of morphine. Occasional ventricular premature contractions occurred in one dog after both opioids and dosages. No dogs vomited or defecated, but all salivated profusely with both opioids. Neuroexcitation occurred in four dogs following each opioid. In conclusion, intravenous hydromorphone induced minimal histamine release and was well tolerated by these conscious healthy dogs.     

Mechanical Ventilation of a Dog with Pentobarbital Intoxication

A 9-year old spayed female American bulldog presented 5 hours after ingesting a portion of a recently euthanized sheep carcass. The dog was comatose, intubated and manually ventilated on arrival. On physical examination, the dog had stable cardiovascular parameters but was hypothermic. Cranial nerve reflexes were absent and spinal reflexes were depressed. Mechanical ventilation was initiated and maintained for 18 hours before spontaneous respiration returned. Elevated serum pentobarbital concentration (19.1 mg/ml) confirmed pentobarbital intoxication as the cause of neurological signs. This is the first report of a dog with pentobarbital toxicity that was successfully managed with mechanical ventilation. Neurologic and functional recovery was complete and the dog was discharged 48 hours after admission. (J Vet Emerg Crit Care 2001; 11(1):33–37)     

Pharmacokinetics of metaflumizone and amitraz in the plasma and hair of dogs following topical application

Controlled laboratory studies have shown that a metaflumizone plus amitraz combination (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) applied topically is effective for the treatment and control of fleas and ticks on dogs. Two studies were conducted to determine the distribution of both metaflumizone and amitraz in the plasma and hair of dogs following treatment at the minimum recommended dose of approximately 20mg/kg of each active ingredient. Six purpose-bred, adult Beagle dogs were used in each study. Plasma or hair samples were collected from each dog just prior to dosing and periodically through 56 days after treatment. Samples were analyzed by HPLC methods validated for the simultaneous determination of metaflumizone and amitraz. Amitraz was detectable (>3.2ng/ml) but not quantifiable (<50ng/ml) in only two plasma samples, collected 1 and 2 days post-treatment from different dogs. Metaflumizone concentrations in plasma were generally detectable (>1.0ng/ml) but not quantifiable (<50ng/ml). Measurable levels were found in one dog 7 days post-treatment, increasing to a maximum of four dogs at 42 days after dosing, with a metaflumizone range of 59-138ng/ml. Analysis of hair samples indicated that both metaflumizone and amitraz were widely distributed at basically similar levels in the hair within 1-day after administration, reaching maximum concentrations between 2 and 7 days post-treatment. Low but quantifiable levels of both compounds were still present on hair at the end of the 56-day study. These studies indicate that the ectoparasitic activity is due to exposure of the parasites to metaflumizone and amitraz on the surface of the host (hair and/or skin), not to exposure via the circulatory system of the host.     

Pharmacokinetics of midazolam administered concurrently with ketamine after intravenous bolus or infusion in dogs

Brown, S.A., Jacobson, J.D., Hartsfield, S.M. Pharmacokinetics of midazolam administered concurrently with ketamine after intravenous bolus or infusion in dogs. J. vet. Pharmacol. Therap. 16 , 419–425. Midazolam, a water-soluble benzodiazepine tranquilizer, has been considered by some veterinary anaesthesiologists to be suitable as a combination anaesthetic agent when administered concurrently with ketamine because of its water solubility and miscibility with ketamine. However, the pharmacokinetics of midazolam have not been extensively described in the dog. Twelve clinically healthy mixed breed dogs (22.2–33.4 kg) were divided into two groups at random and were administered ketamine (10 mg/kg) and midazolam (0.5 mg/kg) either as an intravenous bolus over 30 s (group 1) or as an i.v. infusion in 0.9% NaCl (2 ml/kg) over 15 min. Blood samples were obtained immediately before the drugs were injected and periodically for 6 h afterwards. Serum concentrations were determined using gas chromatography with electron-capture detection. Serum concentrations were best described using a two-compartment open model and indicated a t_½α of 1.8 min and t_½β.p of 27.8 min after i.v. bolus, and t_½α f 1–35 min and t_½β of 31.6 min after i.v. infusion. The calculated pharmacokinetic coefficient B was significantly smaller after i.v. infusion (429 ± 244 ng/ml) than after i.v. bolus (888 ± 130 ng/ml, P = 0.004). Furthermore, AUC was significantly smaller after i.v. infusion (29 800 ±6120 ng/h/ml) than after i.v. bolus (42 500 ± 8460 ng/h/ml, P < 0.05), resulting in a larger Cl_B after i.v. infusion (17.4 ± 4.00 ml/min/kg than after i.v. bolus (12.1 ± 2.24 ml/min/kg, P < 0.05). No other pharmacokinetic value was significantly affected by rate of intravenous administration.     

Bioavailability of three brands of digoxin tablets in dogs

As information on the comparative bioavailability of digoxin tablets in dogs is scarce, three brands of digoxin tablets, commercially available in Belgium, were compared in 6 healthy dogs in a cross-over randomized design. Each dog received 1 mg digoxin on four occasions (once intravenously and 3 times orally). The mean areas under the curve relative to the intravenous value were 80, 71 and 65%. For the 3 oral preparations peak plasma concentrations were reached within 1 hour after dosing and often within 30 minutes. The mean peak concentrations were 11.0, 10.0 and 8.1 ng/ml. The times for 50% dissolution were 4.5, 7.5 and 25 minutes. Although differences between brands were only significant for the dissolution rate, the same ranking order was present for all parameters. It is therefore concluded that it may be advisable not to switch a digitalized dog from one brand to another.     

Plasma LH and progesterone levels before and after ovulation and observation of ovarian follicles by ultrasonographic diagnosis system in dogs

Recently, canine frozen semen has been attracting attention for breeding purposes, and methods of judging ovulation and optimum timing for insemination have become important. As methods of predicting the canine ovulation, vaginal smear, plasma sex hormone levels and ultrasonographic diagnosis system (US) have been investigated in combination, but a standard technique has not yet been established. Therefore, we investigated a method of predicting canine ovulation in dogs by US, and by measuring plasma LH and progesterone (P) levels three times a day. Ovulation could be observed by detecting irregularly shaped ovarian follicles by US in six of 11 dogs (54.5%). In these dogs, the time between the LH peak and ovulation was 24-48 hr, 38.0 hr on average. The P level on the ovulation day was 1.88-2.81 ng/ml, 2.34 ng/ml on average. A value of 1.88 ng/ml was detected in one dog, but the other five dogs showed P levels of 2 ng/ml or higher. The P level on the day before ovulation was 0.8-1.56 ng/ml, 1.12 ng/ml on average. Assuming that ovulation occurred two days after the LH peak in the 11 experimental dogs, the P level was 2.12-4.06 ng/ml, 2.78 ng/ml on average. The period of a high LH level, not less than 10 ng/ml, continued for 12 hr around the LH peak. Based on these findings, to predict ovulation using US and LH level, it would be necessary for the tests to be performed several times a day. In contrast, it was shown that the day on which a plasma P level of 2 ng/ml or higher was detected by the test performed once a day corresponded to the ovulation day.     

S-adenosyl-L-methionine (SAMe) for the treatment of acetaminophen toxicity in a dog

An 8-month-old, spayed female Shetland sheepdog presented 48 hours after ingesting acetaminophen (1 gm/kg body weight). On presentation, the dog was laterally recumbent and hypovolemic. The dog had brown mucous membranes, severe Heinz-body hemolytic anemia, bleeding tendencies, and a red blood cell (RBC) glutathione (GSH) concentration that was 10% of reference values, despite a regenerative erythroid response. Treatment with s-adenosyl-l-methionine (SAMe) as a GSH donor successfully rescued this dog, despite the animal's late presentation after drug ingestion. A loading dose (40 mg/kg body weight) of a stable SAMe salt per os was followed by a maintenance dose (20 mg/kg body weight) sid for 7 days. Additional therapeutic interventions included an intravenous (i.v.) infusion of one unit of packed RBCs (on admission), i.v. fluid support (3 days), and famotidine (7 days) to reduce gastric acidity. Sequential assessment of RBC GSH concentrations and RBC morphology documented response to antidote administration within 72 hours. This case suggests that SAMe may provide a therapeutic option for treatment of acetaminophen toxicosis in dogs capable of retaining an orally administered antidote and maintaining adequate hepatic function for metabolism of SAMe to its thiol substrates.     

A comparative study of the pharmacokinetics of thiopental in the rabbit, sheep and dog

The central arterial pharmacokinetics of thiopental were studied in six rabbits, six sheep and six dogs after a short infusion at approximately 10 mg/kg min. Thiopental was infused to a defined electro-encephalographic endpoint (EEG burst suppression). The time to reach early burst suppression was longer in the dog (3.9 +/- 0.5 min) compared with the sheep (3.0 +/- 0.6 min) and the rabbit (2.5 +/- 0.5 min). The total dose required to produce the same level of EEG activity was higher in the dog (35.9 +/- 6.8 mg/kg) compared with the sheep (24.3 +/- 5.3 mg/kg) and the rabbit (21.6 +/- 6.8 mg/kg). The plasma concentration-time data for each animal was fitted using non-linear regression to a bi- or tri-exponential function. In all animals, the plasma-time profile was best described as a tri-exponential decay. The initial volume of distribution was similar in all three species (rabbit, 38.6 +/- 10.0 mg/kg; sheep, 44.5 +/- 9.1 ml/kg; dog, 38.1 +/- 18.4 ml/kg). The maximum arterial plasma thiopental concentration achieved at EEG burst suppression was higher in the sheep (221.8 +/- 27.9 micrograms/ml) than the dog (164.7 +/- 29.9 micrograms/ml) or the rabbit (112.3 +/- 15.1 micrograms/ml). Thiopental distribution clearance was slower in the sheep (43.6 +/- 15.1 ml/min/kg) compared with the rabbit (110.5 +/- 18.7 ml/min kg) and the dog (97.2 +/- 47.2 ml/min kg). Elimination half-life was extended in the sheep (251.9 +/- 107.8 min) and dog (182.4 +/- 57.9 min) relative to the rabbit (43.1 +/- 3.4 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics and preliminary observations of behavioral changes following administration of midazolam to dogs

The pharmacokinetics of midazolam were investigated following intravenous and intramuscular administration of 0.5 mg of midazolam hydrochloride/kg of body weight to five healthy mixed-breed dogs. One dog also received the same dose of midazolam by oral and rectal routes. The disposition of midazolam following intravenous administration was characterized by very rapid and relatively extensive distribution followed by rapid elimination. Mean (+/- SD) apparent volume of distribution was 3.0 +/- 0.9 l/kg, mean elimination half-life was 77 +/- 18 min, and clearance was 27 +/- 3 ml/kg/min. Following intramuscular administration, absorption was rapid and complete. A mean peak midazolam concentration of 549 +/- 121 ng/ml was reached within 15 min, and systemic availability was over 90% in each dog. Oral administration to one dog resulted in peak midazolam concentrations within 10 min and a systemic availability of 69%. Rectal administration to the same dog yielded very low systemic availability. Midazolam was extensively bound to canine plasma proteins, with the unbound fraction representing less than 4% of the total plasma midazolam concentration. Plasma samples were also assayed for the presence of the major metabolites, 1-OH and 4-OH midazolam. Neither metabolite were detected, probably as a result of rapid elimination of these compounds by hepatic glucuronidation. Behavioral responses to administration of midazolam included initial signs of profound weakness, ataxia and transient agitation followed by a period of quiesence. A normal behavior pattern returned within 2 h of midazolam administration.     

Rebound hyperkalemia in a dog with albuterol toxicosis after cessation of potassium supplementation

Objective

To describe the presentation of rebound hyperkalemia as a delayed side effect of albuterol toxicity in a dog.

Case Summary

A 3-year-old female neutered mixed-breed dog was presented for albuterol toxicosis that led to a severe hypokalemia, hyperlactatemia, and hyperglycemia. The dog also experienced sinus tachycardia and generalized weakness. Treatment was instituted with intravenous fluid therapy and potassium supplementation, and the dog was monitored with a continuous electrocardiogram. Resolution of hypokalemia was documented 12 hours after initial presentation, at which time fluid therapy and potassium supplementation were discontinued. There were no further periods of sinus tachycardia, but instead the dog developed ventricular ectopy with rapid couplets (instantaneous rates of 300/min). An echocardiogram revealed normal cardiac size and function. Twenty-four hours after presentation, the patient developed severe hyperkalemia, despite discontinuation of fluids and potassium supplementation for 12 hours. Serial venous and urinary electrolytes were performed for determination of the fractional excretion of electrolytes. These data confirmed rebound hyperkalemia (7.0 mmol/L), consistent with a markedly increased fractional excretion of potassium, and secondary to the release of potassium from inside the cells. Fluid therapy with dextrose supplementation was provided until 36 hours postpresentation. The hyperkalemia resolved, and the dog was discharged after 44 hours of hospitalization.

New or Unique Information Provided

This case documents rebound hyperkalemia following treatment of albuterol toxicosis in a dog. This case highlights the importance of understanding the distribution of total body potassium when treating serum hypokalemia. Transcellular shifts of potassium, as in the case of albuterol toxicosis, can lead to rebound hyperkalemia even after discontinuation of potassium supplementation. This case further explores the utility of fractional excretion of electrolytes in elucidating the etiology and management of electrolyte disturbances.     

Pharmacokinetics of amoxycillin and the rate of depletion of its residues in pigs

Six pigs were used in a two-period crossover study to investigate the pharmacokinetics of amoxycillin after single intravenous and oral doses of 20 mg/kg bodyweight. Twelve pigs were used to study the residues of the drug in muscle, kidney, liver and fat after they had received daily oral doses of 20 mg/kg amoxycillin for five days. The mean (sd) elimination half life (t1/2beta) and mean residence time of amoxycillin in plasma were 3.38 (0.30) and 3.54 (0.43) hours, respectively, after intravenous administration and 4.13 (0.50) and 4.47 (0.30) hours, respectively, after oral administration. After oral administration, the maximum plasma concentration (Cmax) was 7.37 (0.42) microg/ml and it was reached after 0.97 (0.29) hours. Six days after the last oral dose, the mean concentration of amoxycillin in the pigs' kidneys was 21.38 ng/g and in the liver it was 12.32 ng/g, but no amoxycillin could be detected in fat or muscle; the concentrations of amoxycillin in edible tissues were less than the European Union maximal residue limit of 50 microg/kg.     

The bovine pituitary‐adrenocortical axis and milk yield

Summary

A review is given of the available literature concerning the relationship between the bovine pituitary‐adrenocortical axis and milk yield in dairy cattle. A severe drop in milk yield (more than 50%) can be induced by a single or repeated intramuscular injection of at least 200 IU ACTH or by a single intramuscular injection of 14.6 mg dexamethasone. Sixty minutes after an intravenous injection, both 200 IU ACTH and 100 mg cortisol are equivalent to a plasma cortisol concentration of at least 31 ng/ml. Thus the decrease in milk yield after an intramuscular injection of more than 200 IU ACTH can hardly be induced by cortisol only. The fact that bovine plasma hardly binds any dexamethasone, in sharp contrast with bovine mammary epithelial tissue, is a possible explanation of the special part which dexamethasone plays in milk yield.     

围产期绵羊血浆胰岛素样生长因子-1水平的动态变化及胆酸负荷对其的影响

:6只成年考力代妊娠母羊 ,经 2周适应饲养后随机分为两组。在安装颈静脉血管瘘后 ,一组通过颈静脉瘘管灌注胆酸 ( 2mg/kg) ,另一组同步灌注等量的生理盐水。间隔 1 4天灌注 1次 ,直至分娩。在灌注前和灌注后每天定时采取血样 ,测定血浆IGF -1水平 ,研究绵羊围产期血浆IGF -1的动态变化及胆酸负荷对其的影响。结果表明 ,围产期母羊血浆IGF -1正常水平在 572 .1 0± 2 0 7.1 5ng/ml～ 787.1 2±4 2 .33ng/ml之间 ,没有明显的动态变化规律。但分娩后的IGF -1平均水平显著低于分娩前平均值 ,分别是 639.54± 56.37ng/ml和 70 5.2 1± 52 .2 4ng/ml(P <0 .0 5)。胆酸灌注组母羊妊娠后期血浆IGF -1水平平均为 62 5.2 8± 85.56ng/ml,比对照母羊低 (P <0 .0 5)。本研究提示妊娠后期绵羊母体血浆高水平的IGF -1可能与胎儿生长发育有关 ;胆酸负荷可能影响了妊娠母体的肝功能或胎盘的调节作用     

Presumptive hepatotoxicity and rhabdomyolysis secondary to phenazopyridine toxicity in a dog

Objective – To describe a rare, but potential clinical manifestation of phenazopyridine (PAP) toxicity in a dog. Case Summary – A 6‐year‐old spayed female Chihuahua was evaluated for ataxia and dysphagia after ingestion of 200 mg (66 mg/kg) of PAP hydrochloride. The dog was presented to the hospital with shifting leg lameness involving all 4 limbs, which progressed to reluctance to walk and severe diffuse muscle hyperesthesia. Clinical laboratory abnormalities included marked increases in serum alanine aminotransferase, aspartate aminotransferase, creatine kinase, mild increases in alkaline phosphatase, and increased c‐Tnl‐troponin concentration. Treatment included administration of intravenous fluids, muscle relaxants, pain medications, and hepatoprotectants for 5 days in the hospital, and medical management at home for an additional 5 days. Follow‐up examinations performed 1 and 6 months after initial presentation revealed the dog to be clinically healthy with serum biochemical profiles within reference intervals. New or Unique Information Provided – The purpose of this report is to describe an unusual manifestation of PAP toxicosis in a dog, which has not been previously reported in the literature. A review of the ASPCA Animal Poison Control Center database revealed 347 cases of PAP exposure in dogs during 2000–2009 underscoring the importance of being aware of this toxicity in the dog.     

Comparison of histamine release induced by morphine and oxymorphone administration in dogs

Cardiovascular effects (vasodilatation, hypotension) of morphine administration have been attributed to central actions and peripheral histamine release. In the study reported here, we compared plasma histamine (Hm) concentrations after morphine sulfate and oxymorphone HCl administration in conscious dogs. Five healthy adult dogs (mean body weight, 10.1 kg) were randomly administered morphine (2 mg/kg of body weight, IV) or oxymorphone (0.2 mg/kg, IV) by a 5-second bolus injection at weekly intervals. Venous blood samples (5 ml) were collected from jugular veins before and at 1, 2, 5, 15, 30, and 60 minutes after drug administration. Behavioral changes were recorded. Plasma was analyzed by a radioenzymatic technique, using purified histamine N-methyltransferase as an enzyme catalyst (sensitivity of assay, 40 pg Hm/ml). Mean base-line Hm value for all dogs was 0.55 ng/ml. The mean Hm value was significantly higher (P less than 0.05) than the base-line value at 1, 2, 5, 15, and 60 minutes after morphine administration (531.4, 251.0, 113.0, 31.5, and 1.0 ng of Hm/ml, respectively), but there were no significant increases in histamine values from base-line values at any time after oxymorphone administration. All dogs given morphine and 1 dog given oxymorphone showed excitatory behavior; 2 dogs given morphine and 3 dogs given oxymorphone salivated profusely.     

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.     

Intrathecal morphine overdose in a dog

CASE DESCRIPTION: A healthy 6-year-old 28.5-kg (62.7-lb) spayed female Boxer undergoing surgical repair of a ruptured cranial cruciate ligament was inadvertently administered an overdose of morphine (1.3 mg/kg [0.59 mg/lb]) via subarachnoid injection. CLINICAL FINDINGS: 50 minutes after administration of the overdose, mild multifocal myoclonic contractions became apparent at the level of the tail; the contractions migrated cranially and progressively increased in intensity and frequency during completion of the surgery. TREATMENT AND OUTCOME: The myoclonic contractions were refractory to treatment with midazolam, naloxone, phenobarbital, and pentobarbital; only atracurium (0.1 mg/kg [0.045 mg/lb], IV) was effective in controlling the movements. The dog developed hypertension, dysphoria, hyperthermia, and hypercapnia. The dog remained anesthetized and ventilated mechanically; treatments included continuous rate IV infusions of propofol (1 mg/kg/h [0.45 mg/lb/h]), diazepam (0.25 mg/kg/h [0.11 mg/lb/h]), atracurium (0.1 to 0.3 mg/kg/h [0.045 to 0.14 mg/lb/h]), and naloxone (0.02 mg/kg/h [0.009 mg/lb/h]). Twenty-two hours after the overdose, the myoclonus was no longer present, and the dog was able to ventilate without mechanical assistance. The dog remained sedated until 60 hours after the overdose, at which time its mentation improved, including recognition of caregivers and response to voice commands. No neurologic abnormalities were detectable at discharge (approx 68 hours after the overdose) or at a recheck evaluation 1 week later. CLINICAL RELEVANCE: Although intrathecal administration of an overdose of morphine can be associated with major and potentially fatal complications, it is possible that affected dogs can completely recover with immediate treatment and extensive supportive care.     

Baclofen intoxication in a dog successfully treated with hemodialysis and hemoperfusion coupled with intensive supportive care

Objective: To describe a case of confirmed baclofen intoxication in a dog that was successfully treated with hemodialysis and hemoperfusion (HD/HP) and to report the serum baclofen kinetics. Case summary: A 2.5‐year‐old, 23 kg, spayed female Brittany Spaniel‐mix was treated after ingesting 21‐52 mg/kg of baclofen. The dog was comatose and was receiving manual ventilation at the time of presentation. Extracorporeal HD/HP was started 10 hours after admission. Within 3 hours of starting HD/HP the dog began initiating breaths and was extubated 18 hours after admission. Serial serum samples that were obtained during the first 24 hours of hospitalization were later analyzed for baclofen concentrations. The dog had elevated creatine phosphokinase and liver enzymes that correlated with an agitated recovery period. The dog had thrombocytopenia that resolved by 10 days after presentation. New or unique information provided: HD/HP shortened the baclofen serum elimination half‐life from 5 to 1.5 hours in the initial 2 hours of treatment. The intrinsic elimination rate constant (K_intr) for this dog was 0.138/hour and the total elimination rate constant (K_tot) during the first 2 hours of HD/HP treatment was 0.458/hour. In this dog, HD/HP was an effective method for rapidly decreasing serum baclofen concentration after an acute overdose.     

Blood selenium in naturally fed horses and the effect of selenium administration

Blood Se of adult horses was 26.1, 25.8, and 27.0 ng/ml (mean values at 3 farms), where the Se of food was about 20 ng/g dry substance. Experimental adult horses which received about 41 ng Se/g food showed 45.3 ng/ml blood.At low Se intake suckling foals show higher blood Se than mares, but with high Se intake, the opposite will occur. This is reflected in milk Se, which raises but slowly with rise of mare’s blood Se.Se in blood plasma and in blood corpuscles is on the same level. The effect of various dose levels of Se on blood Se was studied: From 1.5 to 6 mg Se/week, blood Se rose rather linearity; 18 and 30 rag Se/week gave but slightly more effect than 6 mg.     

Carprofen in veterinary medicine. I. Plasma disposition, milk excretion and tolerance in milk-producing cows

Carprofen, a non-steroidal anti-inflammatory drug (NSAID), was injected intravenously in six cows after calving, either as a single or a daily dose of 0.7 mg/kg for five days. Carprofen was well tolerated by the cows at this dose rate, the milk production and biochemical variables remaining within the normal ranges. The plasma elimination half-life of carprofen ranged from 44.5 to 64.6 h after repeated daily injections. These values are longer than those reported for other NSAIDs used in veterinary medicine, e.g. flunixin and phenylbutazone. The volume of distribution and the clearance values calculated after a single intravenous injection amounted to 0.09 l/kg and 9.0 ml/min. The concentration of carprofen in milk collected twice daily (morning and evening) was, in general, below the sensitivity limit of the analytical method (25 ng/ml) up to five days after the last carprofen injection; the concentration of carprofen reached about 30 ng/ml in only a few milk samples collected after the fourth or fifth injection. This indicates that carprofen is poorly excreted in the milk.