Benzathine penicillin G and procaine penicillin G in piglets: comparison of intramuscular and subcutaneous injection.

The disposition of penicillin G in piglets is described after intramuscular or subcutaneous injection of depot preparations. The piglets were injected with 33,000 IU/kg or 100,000 IU/kg benzathine + procaine penicillin G intramuscularly or subcutaneously, or 100,000 IU/kg procaine penicillin G intramuscularly or subcutaneously. Intramuscular injection of benzathine + procaine penicillin resulted in higher maximum concentrations in plasma (Cmax) than did subcutaneous injection. The mean residence time (MRT) of penicillin G was longer when the drugs were injected subcutaneously rather than intramuscularly. The plasma concentration versus time profiles of the subcutaneous injections of benzathine + procaine penicillin revealed secondary peaks, possibly reflecting a certain degree of inflammation at the injection site.

Effects of intravenous infusion of guaifenesin on electroencephalographic variables in pigs.

OBJECTIVE: To investigate the sedative effects of guaifenesin in pigs by use of electroencephalography. ANIMALS: 10 Norwegian Landrace pigs (5 castrated males and 5 sexually intact females). PROCEDURE: Guaifenesin (150 mg/kg of body weight, IV) was administered during a 5-minute period. Using a 2-channel referential electrode configuration, electroencephalograms were recorded before, during, and after infusion of guaifenesin. Changes in spectral edge frequency 95% (SEF), median frequency (MED), and total power were evaluated. RESULTS: After administration of guaifenesin, SEF decreased significantly, and total power increased significantly; however, MED did not change significantly. Analysis of the data did not reveal differences between pigs on the basis of sex. CONCLUSIONS AND CLINICAL RELEVANCE: We concluded that guaifenesin synchronized the patterns of electroencephalograms. This is a strong indication that the drug has a sedative effect in pigs.

The effects of medetomidine and its reversal with atipamezole on plasma glucose, cortisol and noradrenaline in cattle and sheep.

In the present study, we report the effect of medetomidine followed by atipamezole on plasma glucose, cortisol and noradrenaline in calves, cows and sheep. Eight calves, eight lactating dairy cows and eight adult female sheep were included in a crossover trial. The animals were injected i.v. with medetomidine (40 microg/kg), followed 60 min later by atipamezole i.v. (200 microg/kg) or saline. The wash-out period between experiments was 1 or 2 weeks. In every animal, medetomidine induced a marked hyperglycaemia, which was reversed by atipamezole. Cortisol levels increased significantly in cows and sheep, reaching levels 4-8-fold higher than the baseline levels 25-45 min after injection of medetomidine. Atipamezole did not affect the cortisol levels, except in sheep where an increase was observed. Plasma levels of noradrenaline decreased in cows and sheep after medetomidine injection, reflecting the inhibition of sympathetic activity by the drug. After injection of the antagonist, there was a large increase in noradrenaline levels. In conclusion, a high dose of medetomidine does not seem to reduce the overall endocrine stress response in cattle and sheep, which has previously been reported in other species.

A pharmacokinetic study including some relevant clinical effect of medetomidine and atipamezole in lactating dairy cows.

Medetomidine is the most potent and selective alpha2-agonist used in veterinary medicine and its effects can be antagonized by the alpha2-antagonist atipamezole. The pharmacokinetics of medetomidine and atipamezole were studied in a cross-over trial in eight lactating dairy cows. The animals were injected intravenously (i.v.) with medetomidine (40 microg/kg) followed by atipamezole i.v. (200 microg/kg) or saline i.v. after 60 min. Drug concentrations in plasma were measured by HPLC. After the injection of atipamezole, the concentration of medetomidine in plasma increased slightly, the mean increment being 2.7 ng/mL and the mean duration 12.1 min. However, atipamezole did not alter the pharmacokinetics of medetomidine. It is likely that the increase in medetomidine concentration is caused by displacement of medetomidine by atipamezole in highly perfused tissues. The volume of distribution at steady state (Vss) for medetomidine followed by saline and medetomidine followed by atipamezole was 1.21 and 1.32 L/kg, respectively, whereas the total clearance (Cl) values were 24.2 and 25.8 mL/min x kg. Vss and Cl values for atipamezole were 1.77 mL/kg and 48.1 mL/min x kg, respectively. Clinically, medetomidine significantly reduced heart rate and increased rectal temperature for 45 min. Atipamezole reversed the sedative effects of medetomidine. However, all the animals, except one, relapsed into sedation at an average of 80 min after injection of the antagonist.

Pharmacokinetics of medetomidine and atipamezole in dairy calves: an agonist-antagonist interaction.

Medetomidine and atipamezole are licensed for use in dogs and cats in several countries and are highly selective and specific alpha2-adrenoceptor agents. The pharmacokinetics of the agonist medetomidine and the antagonist atipamezole were studied in a cross-over trial in eight dairy calves. The animals were injected intravenously (i.v.) with medetomidine (40 microg/kg i.v.), followed by atipamezole (200 microg/kg i.v.) or saline after 60 min. The wash-out period between experiments was 1 week. Drug concentrations in plasma were determined using HPLC. Atipamezole significantly (P < 0.05) increased the AUMC and MRT of medetomidine due to an increase in the medetomidine concentration when atipamezole was injected i.v. The mean increment in medetomidine concentration was 6.4 ng/mL, increased levels having a mean duration of 39.4 min. Other pharmacokinetic parameters of medetomidine were not significantly altered by atipamezole. Sedative effects of the agonist, and the effectiveness of the antagonist were recorded. All the animals relapsed into sedation on average 80 min after reversal with atipamezole. It is likely that the increase in medetomidine concentration after the injection of atipamezole i.v. results from displacement of medetomidine from alpha2-adrenoceptors in highly perfused tissues.

Reversal of medetomidine-induced sedation in reindeer (Rangifer tarandus tarandus) with atipamezole increases the medetomidine concentration in plasma.

The pharmacokinetics of two potent alpha 2-adrenoceptor agents that can be used for immobilization (medetomidine) and reversal (atipamezole) of the sedation in mammals, were studied in three reindeer (Rangifer tarandus tarandus) in winter and again in summer. Medetomidine (60 micrograms/kg) was injected intravenously (i.v.), followed by atipamezole (300 micrograms/kg) intravenously 60 min later. Drug concentrations in plasma were measured by HPLC. The administration of atipamezole resulted in an immediate 2.5-3.5 fold increase in the medetomidine concentration in plasma. Clearance for medetomidine (median 19.3 mL/min.kg) was lower than clearance for atipamezole (median 31.0 mL/min.kg). The median elimination half-lives of medetomidine and atipamezole in plasma were 76.1 and 59.9 min, respectively. The animals became resedated 0.5-1 h after the reversal with atipamezole. Resedation may be explained by the longer elimination half-life of medetomidine compared to atipamezole.

Evaluation of the dorsal aorta cannulation technique for pharmacokinetic studies in Atlantic salmon (Salmo salar) in sea water.

The antimicrobial drug flumequine was given intravascularly and orally to cannulated and non-cannulated Atlantic salmon (Salmo salar) in sea water at 11 degrees C. The cannulated fish were divided into two groups, which were given flumequine (25 mg/kg) intravenously into the caudal vein (n = 8) and orally via a stomach tube down the oesophagus (n = 8). After a washout period of 2 days, the intravenously administered fish were given the drug orally, and the orally administered fish were given the drug intravenously. Blood samples were taken at different time points after drug administration through a cannula inserted into the dorsal aorta. The fish in the non-cannulated group were either given flumequine intravenously or orally, and blood samples were collected by killing five fish at predetermined time points after administration. The haematocrit values were measured in all the fish daily for 4 days after drug administration and thereafter, in all the collected blood samples throughout the whole experiment. The haematocrit values differed significantly between the cannulated and the non-cannulated fish. We found low haematocrit values and slow drug elimination in the cannulated groups, compared with higher haematocrit values and faster drug elimination in the non-cannulated groups, but further investigations are needed to prove any causal relations of this observation. The volume of distribution (Vd(ss)) was twice as large in the cannulated groups compared with the non-cannulated group, in the fish administered the drug intravenously. In the last part of the elimination phase, the half-lives differed considerably between the cannulated and the non-cannulated groups both after oral and intravenous administration. The slower depletion of the drug concentration in the plasma of the cannulated fish is due to the large Vd(ss) as there are only small differences in clearance (ClT) between the groups. In this study the elimination of flumequine in cannulated Atlantic salmon differed from the elimination of flumequine in non-cannulated Atlantic salmon.

The antimicrobial susceptibility of Staphylococcus species isolated from canine dermatitis.

In a retrospective study, 1538 strains of beta-haemolysin-producing Staphylococcus species isolated from dermatitis in dogs at three veterinary clinical microbiology laboratories in Norway during 1986-87 and 1993-94 were investigated for their antimicrobial susceptibility. None of the strains was resistant to cloxacillin, cephalexin or the quinolones enrofloxacin and ciprofloxacin. More than 96% of the strains were susceptible to trimethoprim-sulphonamide, bacitracin and fucidic acid. Between 67% and 89% of the strains were susceptible to erythromycin, lincosamides, tetracycline, neomycin and chloramphenicol. Only 37.9% of the strains were susceptible to penicillin. The frequency of penicillin resistance increased significantly between the first and second periods, from 46.0% to 58.6%. The frequency of resistance to lincomycin, clindamycin and erythromycin also increased significantly between the first and second periods, from 3.0%, 2.1% and 3.3% to 25.5%, 19.5% and 24.8%, respectively. A moderate increase in resistance to tetracycline was also noted, from 20.4% in the first to 27.6% in the second period. On the other hand, the frequency of resistance to trimethoprim-sulphonamide decreased significantly from 4.1% in the first to 0.9% in the second period. Many different resistance patterns were observed in each period. However, the proportion of multiresistant strains increased from 2.1% in the first to 10.2% in the second period. There was a decrease in resistance to the combination of trimethoprim-sulphonamide and penicillin from the first to the second period. Resistance to the combination of lincosamides and penicillin increased. For the combinations penicillin-tetracycline-lincosamides, penicillin-lincosamides-erythromycin, and penicillin-tetracycline-lincosamides-erythromycin, there was a striking increase in resistance between the first and the second periods.

Xylazine-induced sedation in axis deer (Axis axis) and its reversal by atipamezole.

Eight free-ranging axis deer (Axis axis) were captured in drive nets and injected with xylazine (3.4 +/- 0.1 mg/kg; mean +/- SEM) intramuscularly using a hand-held syringe. Xylazine induced complete immobilization and sedation in three animals, heavy sedation in three, and moderate sedation in two. The mean induction time was 10.4 +/- 1.0 min. The mean rectal temperature, heart and respiratory rates of immobilized animals were 39.2 +/- 0.4 degrees C, 75.5 +/- 6.5 beats/min and 62.1 +/- 4.2 breaths/min, respectively. All the animals were given atipamezole intravenously for reversal. The mean time from injection of xylazine to administration of atipamezole was 37.8 +/- 4.6 min. A dose ratio (w/w) for xylazine:atipamezole-HCl of 10:1 was used. The mean time from injection of atipamezole to mobility was 2.41 +/- 0.58 min. Atipamezole given intravenously effectively antagonized xylazine-induced sedation in axis deer. Only one animal showed signs of overalertness after reversal and no cases of resedation were observed.

Reversal of xylazine-induced sedation in dairy calves with atipamezole: a field trial.

Dairy calves immobilized with xylazine (XYL) were given atipamezole-HCl (ATI) at different XYL:ATI dose ratios (w/w) for reversal and the antagonistic effect of xylazine was evaluated. Control animals received saline for comparison. Intramuscular administration of xylazine (0.139-0.357 mg/kg) induced sedation with complete immobilization in all animals (n = 195) and there were no spontaneous recoveries before injection of atipamezole or saline. Atipamezole was given 10-81 min and saline 25 min after xylazine administration. Intramuscular administration of atipamezole at XYL:ATI dose ratios of 5:2 (n = 11), 10:3 (n = 21), 4:1 (n = 21) and 5:1 (n = 25) effectively antagonized the xylazine-induced immobilization and sedation. The mean times (standard deviation) from injection of atipamezole until the animals were standing for these dose ratio groups were 6.09 (3.12), 5.15 (2.87), 6.35 (2.54) and 7.86 (3.11) min, respectively. The mean time to standing for control animals (n = 11) was 94.1 (3.0) min. Intravenous administration of atipamezole at XYL:ATI dose ratios of 10:3 (n = 7), 4:1 (n = 33), 5:1 (n = 16), 8:1 (n = 27) and 10:1 (n = 9) rapidly reversed the xylazine-induced immobilization and sedation. The mean times (standard deviation) from injection of atipamezole until the animals were standing for these dose ratio groups were 0.98 (0.22), 1.32 (0.48), 1.09 (0.34), 1.39 (0.52) and 1.60 (0.69) min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical capture of free-ranging cattle: immobilization with xylazine or medetomidine, and reversal with atipamezole.

Twenty-nine free-ranging Norwegian cattle were captured with xylazine (n = 20) or medetomidine (n = 9) using a tranquilizing gun, and the time from darting to recumbency (induction time) was recorded. Twenty-eight animals were given atipamezole IV 15-100 min after darting, and the effects of the antagonist were evaluated. Blood samples (n = 19) for haematology and serum chemistry were collected within 10 min after immobilization was induced. Xylazine (0.55 +/- 0.18 mg/kg; mean +/- SD; n = 18) or medetomidine-HCl (0.039 +/- 0.10 mg/kg; n = 8) induced complete immobilization after a single darting with sternal or lateral recumbency, the induction times being 9.6 +/- 3.8 and 12.0 +/- 6.8 min, respectively. No difference in the clinical effects of the two drugs was observed. Rapid reversal was achieved with 0.057 +/- 0.017 and 0.077 +/- 0.019 mg/kg of atipamezole-HCl in xylazine- and medetomidine-treated animals, respectively. All the animals stood within 2 min after IV administration of the antagonist. Seven animals showed signs of excitement shortly after reversal, but these side-effects were of brief duration. Heavy resedation with relapse into recumbency was seen 3-4 h after reversal in two cows captured with xylazine, while moderate resedation was observed in two medetomidine-treated animals 2 h after reversal. Except for the plasma glucose concentration, which was elevated in both xylazine- and medetomidine-treated animals, the mean values of the haematological and plasma chemical parameters were within the reference ranges established for Norwegian cattle.(ABSTRACT TRUNCATED AT 250 WORDS)

Prescribing of drugs for food-producing animals in Norway. Information about withdrawal times.

The prescribing of drugs for food-producing animals in Norway was investigated with special emphasis on written information given about withdrawal times. The study was designed as a cross-sectional prescription survey. Of 1518 prescriptions for food-producing animals, it was concluded that 1224 of the prescriptions were for drugs requiring withdrawal times for meat, milk or eggs. Of these 1224 prescriptions, 82.8% were for veterinary preparations, 6.6% were for human preparations and 10.6% were for other drugs. For 20.8% of the prescriptions, information about withdrawal time(s) was missing. For prescriptions for veterinary preparations this figure was 5.9%, and for prescriptions for human preparations and other drugs 95.1% and 90.8%, respectively. For veterinary preparations approved for the intended species, as many as 99.2% gave information about withdrawal times on the drug container label. Lack of information about withdrawal times might give rise to drug residues in food for human consumption and thus pose a potential hazard to human health.

Prescribing of veterinary and human preparations for animals in Norway. Was the preparation approved for the animal species for which it was prescribed?

The prescribing of drugs for use in veterinary medicine in Norway was investigated through a cross-sectional survey. Of the 8741 prescriptions issued for animals included in this study 22% were for drug use in veterinarians' practices. Drugs from all but one therapeutic group were prescribed for use in animals. On average, 49% of the prescriptions were for veterinary preparations, 43% were for human preparations, and 8% were for formulations prepared by pharmacies. Of prescriptions for specific animal species, 27% of the preparations were not approved for the intended animal species. The corresponding figures for prescriptions of veterinary and human preparations were 7% and 41%, respectively. Of prescriptions for production animals 17% of the preparations were not approved for the intended animal species, and for pets this figure was 30%.

Immobilization of mink (Mustela vison) with medetomidine-ketamine and remobilization with atipamezole.

Four groups of mink were immobilized with medetomidine-HCl (MED) 0.1 mg/kg + ketamine (KET) 5 or 7.5 mg/kg at different ambient temperatures. The induction time, degree of immobilization and analgesia, rectal temperature, heart and respiration rates were recorded at intervals throughout the immobilization period. The animals were then given atipamezole-HCl (ATI) 0.5 mg/kg for reversal at different times after injection of MED/KET and the effects of the antagonist were evaluated. Subcutaneous administration of MED/KET induced complete immobilization in all 20 animals, and the highest dose was considered suitable for major surgery. Prolonged immobilization at low ambient temperatures (-10 to +5 degrees C) caused severe hypothermia in all animals. The mean rectal temperature had dropped to 37.8 degrees C and 32.1 degrees C at 15 and 85 min, respectively, after injection of MED/KET, significantly lower than the corresponding values for animals immobilized at room temperature. Intramuscular administration of ATI 20 or 40 min after injection of MED/KET rapidly remobilized the animals without apparent side-effects. Administration of ATI to animals recovering spontaneously 90 min after injection of MED/KET induced thermogenesis (shivering) in animals immobilized at a low ambient temperature, while no such effect was seen in animals immobilized at room temperature. One hour after injection of ATI, the rectal temperatures of all treated animals had returned to normal and there were no signs of abnormal behaviour.

An evaluation of the information given on veterinary prescriptions in Norway. Compliance with the legal regulations.

Compliance with Norwegian legal regulations for veterinary prescriptions was investigated and evaluated. The study was designed as a cross-sectional prescription survey, and the prescriptions were recorded in Dbase III. Of the 6505 written and telephone prescriptions collected only about one in five fulfilled the legal requirements, namely, giving information about the animal species the drug was intended for, indication for the prescribed drug and directions for use. On average 86% contained information about the animal species, while 26% and 80%, respectively, contained formation about the indication for the prescribed drug and directions for use. The number of prescriptions on which indication and directions for use were given, was significantly higher for written prescriptions than for telephone prescriptions, and for prescriptions of human preparations compared with prescriptions of veterinary preparations. For pets, the number of prescriptions containing directions for use was significantly higher than for production animals. The proportion of prescriptions for pets giving a statement of the indication was not significantly different from prescriptions for production animals.

Utilization of dichlorvos and trichlorfon in salmonid farming in Norway during 1981-1988.

The main objectives of this investigation were to quantify the use of dichlorvos and trichlorfon in the treatment of salmon lice infestations, to evaluate the prescribing of these drugs, and to estimate possible changes in the salmon lice problem by use of drug statistics. This study has shown that the use of trichlorfon increased from 4.9 tons in 1981 to 28.3 tons in 1985. This figure declined to 3.2 tons in 1988. The use of dichlorvos increased from 0.3 tons in 1986 to 3.2 tons in 1988. The change in the prescribing from trichlorfon to dichlorvos has dramatically reduced the pollution caused by these substances in the marine environment. Moreover, if necessary safety rules are observed, this change reduces the exposure of the workers on fish farms to these drugs, and also reduces the possibilities of intoxications of the fish during the treatment procedure. The sales figures of dichlorvos and trichlorfon, related to the calculated biomass of farmed salmonids in the sea, indicate a dramatic increase in the salmon lice problem.