bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intravenous and oral administration of enrofloxacin in dogs
Authors: KÜNG K. , RIOND J.‐L. , WANNER M.
Published: April 2008

Rung, K., Riond, J.‐L. & Wanner, M. Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intravenous and oral administration of enrofloxacin in dogs. J. vet

Four dogs were given 5 mg/kg body weight enrofloxacin intravenously (i.v.) and orally (p.o.) in a cross‐over study. Plasma concentrations of the active ingredient enrofloxacin and its main metabolite ciprofloxacin were determined by a reversed phase liquid chromatographic method. Pharmacokinetic parameters of both substances were calculated by use of statistical moments and were compared to those of enrofloxacin described in the veterinary literature. Mean enrofloxacin t½λZ was 2.4 h, mean Cls was 27.1 ml/min‐kg, and mean Vss was 7.0 1/kg. After i.v. and p.o. administration, concentrations of ciprofloxacin exceeding minimal inhibitory concentrations of several microorganisms were reached (Cmax= 0.2 ng/ml, max = 2.2 h after intravenous administration; Cmax= 0.2 (ig/ml, tmax= 3.6 h after oral administration). A considerable part of the antimicrobial activity is due to ciprofloxacin, the main metabolite of enrofloxacin.
Effects of dietary variations on plasma concentrations of oral flukicides in sheep
Authors: TAYLOR S. M. , MALLON T. R. , BLANCHFLOWER J. , KENNEDY D. G. , HEWITT S. A.
Published: April 2008

Groups of parasite‐free lambs which were either housed and fed hay arid concentrates or were grazing on pasture were dosed with the oral flukicides rafoxanide and triclabendazole and subsequent plasma Concentrations moni‐tored. Peak plasma concentrations and areas under curves (AUC) of both chemicals were significantly reduced in the grazing compared with the housed lambs. In order to investigate the observation similar groups of lambs were dosed orally with chromium EDI'A and faecal throughput estimated. I t was observed that the rate of throughput was greater in the grazing lambs, leading to the conclusion that the differences in plasma concentrations of the flukicides was caused by a reduction in their absorption in the grazing lambs. The implications on flukicide efficacy and dose rates are discussed.
Urinary excretion of metals during treatment with D‐penicillamine and 2‐mercaptopropionylglycine in normal and cystinuric dogs
Authors: HOPPE A. , DENNEBERG T. , FRANK A. , KÅGEDAL B. , PETERSSON L. R.
Published: April 2008

Urinary excretion of nietals during treatment with 2‐rnercaptopropioiiylglycine (2‐MPG) was studied in 11 normal and 20 cystinuric male dogs. 'Ihe results

were compared with those obtained during D‐penicillamine treatment.

Twenty‐four‐h urine and morning samples of urine were taken for determina‐

tion of 13 metals before and during treatment. After single intravenous and oral

D‐penicillamine treatment of the normal dogs, significant increases were found

in the 24‐11 urinary excretion of Ca, Cu and Zn. Oral intake of D‐penicillamine

increased the excretion of Ch, Cr, Fe and Mg as well. No effect on renal metal

excretion was observed after single intravenous and up to 2 months of daily oral

treatment with 2‐MPG.

In 14 cystinuric dogs no effect was found after single intravenous and oral

administrations of 2‐MPG. However, after oral treatment of six cystinuric dogs

with 2‐MPG for 2–4 months, significantly increased excretions of Ca and Mg

were found. Fourteen of the cystinuric dogs were also investigated after 2–6

years of continuous 2‐MPG treatment, and after this period no significant

elevation in the urinary excretion of metals was found. The present study shows

that in contrast to D‐penicillamine, 2‐MPG does not increase the urinary

excretion of metals to any appreciable extent. Observed increases in the

excretion of Ca and Mg seemed to be a temporary effect only.
Effects of dopamine receptor agonists on food intake and rumen motility in dwarf goats
Authors: KAYA F. , DUIN C T M VAN , MIERT A. S. J. P. A. M. VAN
Published: April 2008

Kaya, F., Van Duin, C.T.M. & Van Miert, A.S.J.P.A.M. Food intake and rumen motility in dwarf goats. Effects of some dopamine receptor agonists. J. vet. PharmacolTherap, 17, 120–126.

In ruminants, the dopaminergic regulation of feeding behaviour has not been investigated. Therefore, the effects of dopamine receptor agonists and antagonists on food intake and forestomach motility were studied in dwarf goats Goats treated i.v. with bromocriptine (1 μg or 2.5 μg/kg body wt/min during 10 min) ate less food than when treated with saline. This inhibitory effect on food intake could not be prevented by the peripheral dopamine receptor antagonist domperidone (0.5 mg/kg body wt i.v.). In contrast, dopamine (i.v. 20 μg/kg body wt/min during 15 min), levodopa (i.v. 40 μg/kg body weight during 10 min), apomorphine (i.v. 2 μg/kg body wt/min during 10 min) and lisuride (i.v. 0.2 μg/kg body wt/min during 15 min and 0.5 μg/kg body wt during 10 min) failed to modify food intake. Given in association with benserazide, a decarboxylase inhibitor (i.v. 20 μg/kg body wt/min during 10 min), levodopa was still inactive as an anorectie agent. Levopoda, bromocriptine and lisuride administered at similar dose rates to those which were used in the food intake experiments, induced some clinical signs including inhibition of forestomach contractions. The inhibition of rumen contractions induced by these drugs was completely antagonized by domperidone pretreatment. These results, together with earlier in vivo and in vitro observations, suggest that the inhibitory effects of dopamine receptor agonists on forestomach contractions are due to interactions with peripheral dopaminergic receptors. The change in smooth muscle tension, which leads to a change in the signals transmitted via vagal afferents to the central nervous system, probably does not modify feeding behaviour in dwarf goats. Furthermore, i.v. infusion of lisuride induced rumination when the inhibition of the forestomach contractions was prevented by domperidone; this effect may involve α2‐adrenoceptor activation.
Effects of feed additives and veterinary drugs on aldosterone production and release by porcine adrenal cells in vitro
Authors: JAGER L. P. , GRAAF G. J. DE , WIDJAJA‐GREEFKES H. C. A. , ACCORD‐BURLESON C. C. F. , DUNGEN H. M. VAN DEN , BAARS A. J.
Published: April 2008

The preparation of suspensions of porcine adrenocortical cells is described. Within the conditions adopted, the cell suspension responded to various agents as expected. It was possible to screen drugs (standard range 0.3–100 μM, incubation period 1 h) for actions on the productionhelease of aldosterone by the cortical cells using 1 μM deoxycorticosterone as substrate. Progesterone, pregnenolone or corticosterone were also used as substrates. Feed additives of the quinoxaline type induced a slowly developing inhibition of aldosterone production/release by the cell suspension, which was virtually irreversible. During the standard 1 h incubation period inhibitions of up to 22 ± 2% of control were observed, which increased upon prolongation of the incubation by 2 h. With 100 μM cyadox the inhibition increased from 19 ± 2% to 35 ± 2% with prolonged incubation. Ten nitrofuran compounds exerted a more rapidly developing inhibition (by up to 79 ± 1% of control) of aldosterone production/release, which was reversible. A submaximal inhibition with 10 μM furazolidone of 21 ± 5% increased to 40 ± 1% with longer incubation. The concentrations at which these compounds exerted this effect in vitro were well below the peak blood plasma concentrations encountered after administration of the drugs in therapeutic doses. Polyether‐antibacterials/ionophores rapidly inhibited aldosterone production/release (to 26 ± 1% of control) and this effect was completely reversible. The nitroimidazole compounds tested did not affect aldosterone production/release when deoxycorticosterone or progesterone were used as substrates. With use of corticosterone and to a lesser extent with pregnenolone as substrates a clear inhibition (to 73 ± 3% of control) of aldosterone production was obtained. Amprolium in concentrations up to 100 μM, with deoxycorti‐costerone as substrate, did not induce a significant change in aldosterone production/release by the suspension of adrenocortical cells. In the same dose range tylosin and roxarsone induced a small but significant inhibition (by up to 10 ± 3% of control) of aldosterone production/release, which was not dose‐dependent. It is concluded that a wide range of growth‐promoting drugs may be able to change aldosterone productionhelease in the animal.
A field study of the ivermectin sustained‐release bolus in the seasonal control of gastrointestinal nematode parasitism in first season grazing calves
Authors: CLAEREBOUT E. , HOLLANDERS W. , COCK H. DE , VERCRUYSSE J. , HIDERSON H.
Published: April 2008

The effect of an ivermectin sustained‐release bolus (I‐SRB) on the epidemiology of nematode parasites and on calf productivity was evaluated in a field trial under Northwestern European conditions. Twenty parasite‐naive female Friesian calves (principals) aged 5–9 months were used together with six male Friesian tracer calves. Principal calves were allocated by restricted randomization on day 0 body weight to either an untreated control group or a group given one I‐SRB, designed to deliver 12 mg ivermectin per day for 135 days, orally on day 0. Each group was grazed on adjacent paddocks, naturally contaminated with parasitic nematode larvae, from 13 May 1991 (day 0) until housing on 30 September (day 140). Body weights of principal calves were recorded and individual blood and faecal samples taken at regular intervals throughout the trial. Pasture nematode contamination was monitored by larval counts on herbage and by worm counts of tracer calves grazed on each paddock from day 126 to day 140. Nematode contamination levels on the control paddock did not rise until the end of the grazing season, as a result of a mid‐summer drought period. The period of exposure to a high larval challenge was too short to provoke body weight losses and clinical parasitic gastroenteritis in control calves. Use of the I‐SRB resulted in zero faecal egg counts of trichostrongyles during the whole pasture season, thereby preventing a build‐up of parasitic gastrointestinal nematodes on pasture. During the second grazing season no signs of parasitic gastroenteritis were detected in any animal, but an outbreak of parasitic bronchitis (PB) was observed in both experimental groups, indicating that PB can occur in older cattle regardless of the control measures taken to prevent clinical parasitism during the first grazing season.
Disposition of parathion after dermal application in pigs*
Authors: BRIMER L. , GYRD‐HANSEN N. , RASMUSSEN F.
Published: April 2008

Pharmacokinetic parameters of parathion were studied in pigs after intravenous (i.v,) and dermal administration of unlabelled and ‘“C‐parathion. Plasma concentration‐time data were subjected to non‐compartmental analysis. Intravenous injection studies showed a mean residence time (MRT) of 2.15 h, a body clearance (ClB) of 4.4 l/kg/h and a volume of distribution (Vss) of 9.8 l/kg. Dermal application led to a mean absorption time (MAT) of 78 h. and a bioavailability of 9.9%. Plasma levels of 14C‐parathion (parathion + metabolites) were much higher and more persistent than those of parathion itself. After i.v. administration, recovery of 14C‐parathion from urine plus faeces was almost 100% within 3 d, while it was less than 20% after dermal application. Ten days after dermal application high I4C concentrations remained in the back skin, i.e. the application area. In skin samples from areas where contamination from the application area could not have occurred, the 14C‐parathion concentration was as low as 2 μg/g. It is concluded that in view of the low dermal bioavailability for organophosphorus insecticides it is unlikely that pour‐on preparations containing these insecticides reach the ectoparasites through absorption and systemic distribution, but rather that this happens after spreading on the surface of the skin.
Pharmacokinetics of thiopentone in the horse
Authors: ABASS B. T. , WEAVER B. M. Q. , STADDON G. E. , WATERMAN A. W.
Published: April 2008

Abass, B.T., Weaver, B.M.Q., Staddon, G.E., Waterman, A.W. Pharmacokinetics of thiopentone in the horse. J. vet. Pharmacol. Therap. 17, 331–338.

The pharmacokinetics of thiopentone sodium administered intravenously as a single dose (11 mg/kg) were studied in acepromazine pre‐medicated horses and ponies in which anaesthesia was maintained with either halothane (Group 1) or isoflurane (Group 2). The results showed that the disposition kinetics of thiopentone in horses and ponies were best described by a three‐compartment open model. In plasma, a very short initial distribution phase in both horses and ponies, half‐life 1.4 ± 1.2 min (mean ± SD) and 1.3 ± 0.7 min, respectively, was obtained, which was followed by a second comparatively slower redistribution phase, half‐life 16 ± 12 min and 11 ± 5 min, respectively. The volume of distribution for the drug was large, especially in the ponies which received isoflurane (1127 ± 86 ml/kg). compared to the horses which received halothane (742 ± 89 ml/kg). The drug had a somewhat shorter elimination half‐life in the horses (147 ± 21 min) than in the ponies (222 ± 44 min), but no obvious difference in clearance of the drug was observed between the horses (3.5 ± 0.5 ml/min/kg) and ponies (3.6 ± 0.8 ml/min/kg).
Disposition of ciprofloxacin following intravenous administration in dogs
Authors: ABADÍA A. R. , ARAMAYONA J. J. , MUÑOZ M. J. , DELFINA J. M. PLA , SAEZ M P , BREGANTE M A
Published: April 2008

The pharmacokinetics of ciprofloxacin (CIP) following intravenous administration m dogs nave been mvestisated. The drug was administered at three doses (2.5,5 and 10 mg/kg body weight) and was assayed in biological fluid samples (plasma and urine) by an HPLC method. The plasma concentration‐time curves ere best described by a two‐compartment open pharmacokinetic model. The was widely distributed (Vd(area)almost 3 1/kg), being distributed in the dog more rapidly than in other species (t1/2(λ1)3 min approximately). The elimination half‐life (t1/2λ2)) was 129–180 min which is similar to values obtaine in other species. The unchanged drug eliminated in urine was less than 37% of the administered dose, which is less than the values obtained in humans, calves and pigs. The glomerular filtration rate and the renal clearance of CIP in the dog suggest that renal elimination probably occurs mainly by glomerular filtration. The results showed that the pharmacokinetics of CIP, as in other species, was linear in dogs in the dose range studied.
An image analysis system: an objective and accurate alternative for reading the agar diffusion test
Authors: SCHOEVERS E. J. , TERLOU M. , PIJPERS A. , VERHEIJDEN J. H. M.
Published: April 2008

Schoevers, E.J., Terlou, M., Pijpers, A., Verheijden, J.H.M. An image analysis system: an objective and accurate alternative for reading the agar diffusion test. J. vet. Pharmacol Therap. 17, 38–42.

A computerized image analysis system (IAS) has been used to develop a new method for reading the agar diffusion test automatically. In four experiments a total of 88 porcine plasma and 95 urine samples were screened for oxytetra‐cycline by the agar diffusion test. The inhibition zones were measured by hand and by the IAS directly from the bioassay plate and by the IAS from the photonegative taken from the plate. Both methods were positively correlated with the hand method for plasma (0.9716, 0.9669) and urine (0.9878, 0.9731) in the range tested for 0.1 to 2.0 (m̈/ml. Moreover, the coefficient of variation and the day‐to‐day‐variation amounted to 1,72% and 1.47% respectively, for the method by hand and 1.10, 1.54% and 0.27, 0.38% respectively, for the IAS methods. It is concluded that the IAS method is an objective and accurate alternative for reading the agar diffusion test.
Pharmacokinetics, oral bioavailability and tissue distribution of azithromycin in cats
Authors: HUNTER R.P. , LYNCH M.J. , ERICSON J.F. , MILLAS W.J. , FLETCHER A.M. , RYAN N.I. , OLSON J.A.
Published: April 2008

Azithromycin is the first of a class of antibiotics classified as azalides. In an initial experiment four cats were given a single dose of azithromycin 5 mg/kg orally (p.o.), followed 2 weeks later by a single intravenous bolus (i.v.) dose of 5 mg/kg. Subsequently, six cats were given [14C]azithromycin p.o. in a single dose of 5.4 mg/kg for the study of tissue distribution and metabolism. In both experiments, serial blood samples were collected and the plasma assayed for unchanged azithromycin to determine various pharmacokinetic parameters. After p.o. administration, bioavailability was 58% and absorption rapid with atmaxof 0.85±0.72 h and a Cmaxof 0.97 ± 0.65 μg/mL The harmonic mean terminal t1/2after i.v. administration was 35 h. Tissue half‐lives varied from 13 h in fat to 72 h in cardiac muscle. Three metabolites were identified in bile. Unchanged azithromycin accounted for 100% of the total radioactivity in lung and skin tissues when assayed. In comparison with other species, the bioavailability in cats is higher than in humans but lower than in dogs. As in the dog, > 50% of the azithromycin‐related material in feline bile was unchanged azithromycin.
Pharmacokinetics of flunixin and its effect on prostaglandin F2αmetabolite concentrations after oral and intravenous administration in heifers
Authors: ODENSVIK K.
Published: April 2008

Flunixin meglumine (FM) was administered either orally as granules or intravenously to six heifers in a two period crossover study. Single doses of 2.2 mg/kg body weight were used. Pharmacokinetic variables were calculated using statistical moment methods. The effect exerted by flunixin was measured as changes in the basal plasma concentration of the main metabolite of prostaglandin (PG) F2α. After oral FM the arithmetic means of pharmacokinetic variables were:MRT= 12.7 h;MAT =6.3 h;Cmax= 0.9 μg/mL;tmax= 3.5 h. The bioavailability was 60% and the mean half‐life (harmonic mean) was 6.2 h. Oral administration of FM inhibited as effectively as intravenous administration the prostaglandin biosynthesis. The concentration of the PG metabolite decreased almost as rapidly as after intravenous administration. The duration of the effect was prolonged and the PG metabolite concentration was significantly lower between 10 and 30 h after oral than after intravenous administration. The results indicate that oral dosing of flunixin, in the form of granules, can be an alternative to intravenous administration for therapeutic use in cattle.
Kinetic disposition of triclabendazole in buffalo compared to cattle
Authors: SANYAL P.K.
Published: April 2008

Concentrations of triclabendazole sulfoxide and its sulfone metabolite in plasma were measured in buffalo and cross‐bred cattle after single intraruminal administration of triclabendazole at two different doses. Plasma concentrations of both metabolites were significantly lower in buffalo than cattle at both doses, which resulted in a smaller area under the concentration‐time curve, a lower concentration maximum and a lower relative bioavailability. Thus, the recommended doses of 12 mg/kg body weight for the treatment of bubaline fascloliasis may not be valid for buffalo because of the substantially lower uptake of the drug in this species.
Fluoroquinolones in animal health
Authors: BROWN S. A.
Published: April 2008

The fluoroquinolones are a series of synthetic antibacterial agents that are undergoing extensive investigation for both human and veterinary use in the treatment of a variety of bacterial infections. These agents work through the inhibition of DNA gyrase, interfering with the supercoiling of bacterial chromosomal material. As a result, these agents are rapidly bactericidal primarily against gram‐negative bacteria, mycoplasma, and some grampositive bacteria, with most having little to no activity against group D streptococci and obligate anaerobic bacteria. Resistance develops slowly and is almost always chromosomal and not plasmid‐mediated. However, development of resistance to the fluoroquinolones and transfer of that resistance among animal and human pathogens have become a hotly debated issue among microbiologists. The fluoroquinolones are a current antimicrobial class whose use in veterinary medicine is being scrutinized. From a pharmacokinetic perspective, these agents are variably but well absorbed from the gastrointestinal tract and almost completely absorbed from parenteral injection sites, and they are well distributed to various tissues in the body. The fluoroquinolones are metabolized and renally excreted, with many of them having approximately equal excretion by the hepatic and the renal excretory systems. The primary toxicity observed at therapeutic doses involves the gastrointestinal system and phototoxicity, although at higher doses central nervous system toxicity and ocular cataracts are observed. Administration to immature animals may result in erosive arthropathies at weight‐bearing joints, and administration of high doses to pregnant animals results in maternotoxicity and occasionally embryonic death. The fluoroquinolones are approved for indications such as urinary tract infections and soft tissue infections in dogs and cats and colibacillosis in poultry. Approval for bovine respiratory disease in the United States is being sought. Other indications for which the fluoroquinolones have been used in animal health include deep‐seated infections, prostatitis, and other bacterial infections resistant to standard antimicrobial therapy.
Pharmacokinetics of oxcarbazepine in the dog
Authors: SCHICHT S. , WIGGER D. , FREY H.‐H.
Published: April 2008

Oxcarbazepine has been proven to be a promising new antiepileptic drug for the treatment of human epilepsy. Unlike carbamazepine, it is not oxidatively metabolized in humans, and therefore causes almost no induction of hepatic enzymes at clinically effective dosages. Though showing similar efficacy to carbamazepine, it has been reported to cause significantly fewer side‐effects. It was the purpose of the present study to determine whether oxcarbazepine might be suitable for the treatment of canine epilepsy. In single‐dose experiments, 40 mg/kg oxcarbazepine as a suspension was administered to seven dogs via gastric tube. Plasma concentrations reached peak concentrations of 2.4‐8.8 μg/mL at about 1.5 h and declined with an elimination half‐life of approximately 4 h. The corresponding concentrations of its metabolite, 10.11‐dihydro‐10‐hydroxycarbamazepine, did not exceed 1 μg/mL. During continued treatment for 8 days, doses of 30 and 50 mg/kg were administered orally in capsules to two dogs three times a day. Plasma concentrations showed a pronounced decline from day 3. and the terminal half‐life decreased to 2 h and 1 h. This is considered to be the result of oxcarbazepine inducing its own metabolism. The data reveal that oxcarbazepine, compared with former results with carbamazepine, offers no advantage for the treatment of epileptic dogs.
Pharmacokinetics and anti‐trichomonal efficacy of a dimetridazole tablet and water‐soluble powder in homing pigeons (Columb a livia)
Authors: INGHELBRECHT S. , VERMEERSCH H. , RONSMANS S. , REMON J. P. , DEBACKER P. , VERCRUYSSE† J.
Published: April 2008

The anti‐trichomonal efficacy and pharmacokinetics of dimetridazole were investigated in the homing pigeon (Columba livia). Dimetridazole was formulated for drinking water medication and as a prolonged‐release tablet. To suppress a Trichomonas gallinae infection successfully, medicated drinking water containing dimetridazole (400 mg/L) had to be administered for at least 3 days. A two‐day treatment with a dimetridazole tablet (20 mg/tablet) in fasted, as well as in fed, pigeons was shown to be ineffective. After intravenous administration of 20 mg dimetridazole, the drug plasma concentration‐time profile fitted a one‐compartment open model with a mean half‐life of 3.9 h. The absolute bioavailability of the tablet in fasted pigeons was 83.8%. The bioavailability of the tablet administered with food was reduced by 20%. Dimetridazole was rapidly metabolised to (1‐methyl‐5‐nitroimidazol‐2‐yl)methanol.
Pharmacokinetic‐pharmacodynamic model for spiramycin in staphylococcal mastitis
Authors: RENARD L. , SANDERS P. , LAURENTIE M. , DELMAS J. ‐M.
Published: April 2008

Simultaneous pharmacokinetic‐pharmacodynamic (PK/PD) modelling for spiramycin in staphylococcal infections of the mammary gland of cows was used to predict the efficacy of spiramycin. A differential equation derived from the Zhi model was fitted to anin vitrokilling curve and post‐antibiotic effect determination. A seven‐compartment PK model, in which 4 compartments representing each quarter of the mammary gland which was considered to be the effect compartment, was included. The PD model linked to the PK model was able to describe thein vivospiramycin effect againstStaphylococcus aureus. The parameters calculated fromin vitrodata predicted a rapid decrease for the first 12‐24 h, and regrowth within72h following the treatment, whereasin vivothe bacterial effect was much less after 24 h than that predicted by thein vitrodata. PK/PD modelling permitted the simulation of various doses to optimize the efficacy of the antibiotic, taking into account such dynamic parameters as bacterial growth rate constant, bacterial killing rate constant and the Michaelis‐Menten type saturation constant. An optimal dosage regimen of 20 000 IU/kg per day for 3 days was predicted for the treatment ofStaphylococcus aureusmastitis.
The actions of medetomidine may not be mediated exclusively by α2‐adrenoceptors in the equine saphenous vein
Authors: BRYANT C. E. , CLARKE K. W.
Published: April 2008

Spirals of endothelially denuded equine saphenous vein were used to study the pre‐ and post‐junctional effects of medetomidine in vitro. The pD2 values were calculated for noradrenaline (6.7 /pm 0.1), phenylephrine (5.6 /pm 0.1), BHT 920 (6.2 /pm 0.2) and UK 14304 (5.7 /pm 0.2). Medetomidine produced a biphasic response, with a pD21 of 8.2 /pm 0.1 and a pD22 of 5.7 /pm 0.1 in the equine saphenous vein (n = 6). Prazosin (10−7 m) significantly shifted the second phase of the medetomidine concentration‐response curve to the right (pD21 was 8.1 /pm 0.2 and pD22 was 5.0 /pm 0.2, P < 0.05). Rings of equine saphenous vein were electrically stimulated to investigate the pre‐junctional effects of medetomidine. Increasing concentrations of the α2‐adrenoceptor agonist BHT 920 reduced the response to electrical stimulation in a concentration dependent manner to a maximum of 40 /pm 5%. whereas medetomidine (0.1‐100 nm) caused a concentration dependent enhancement to a maximum of 490 /pm 150%. These results suggest α1‐ and α2‐adrenoceptors are functional in the equine saphenous vein, but that medetomidine is not acting exclusively as an α2‐adrenoceptor agonist.
Binding of sulphamethazine to pig plasma proteins and albumin
Authors: MUNSEY T. , GRIGG R. E. , McCORMACK A. , SYMONDS H. W. , BOWMER C. J.
Published: April 2008

The interaction of sulphamethazine (SMZ) with pig plasma proteins and albumin was studied by ultrafiltration and equilibrium dialysis. Binding to pig plasma proteins was monophasic (affinity ˜9.0 mol/L × 103) and the main binding protein was albumin. At 37ΩC and pH 7.4, the affinity of SMZ for albumin was about 8.0 mol/L x 103 and the number of binding sites was estimated as 1.4. Increasing the temperature from 4 to 45ΩC resulted in a sevenfold decrease in affinity, and increasing pH from 6.0 to 8.0 enhanced affinity for pig albumin ten‐fold. The free energy of binding (‐ΔG) and enthalpy change (‐ΔH) were around 5.5 and 5.1 Kcal/mol, respectively. The total entropy change (ΔS) was small and positive, around 2 cal/mol/°K. Studies with the fluorescent probes warfarin and dansylsarcosine, suggest that these bind to separate sites on porcine albumin. SMZ displaced both probes and inhibited the deacetylation of p‐nitrophenyl acetate by pig albumin. We conclude that: (1) binding of SMZ to pig plasma proteins and albumin is weak; (2) the interaction with albumin is exothermic and enthalpy driven, and (3) pig albumin, like other mammalian albumins, appears to possess discrete binding sites for warfarin and dansylsarcosine. SMZ interacts with both these loci.
Concentrations of tinidazole in gingival crevicular fluid and plasma in dogs after multiple dose administration
Authors: SARKIALA‐KESSEL E. M. , JÄRVINEN A. , NOKELAINEN M. , ASIKAINEN S.
Published: April 2008

Tinidazole 15 mg/kg was administered to eight Beagle dogs with gingivitis or periodontitis twice daily for 3 days. Tinidazole concentrations in blood and gingival crevicular fluid (GCF) were measured 1,3,6 and 9 h after the morning dose each day. The concentration of tinidazole was determined by high performance liquid chromatography (HPLC). The mean concentration of tinidazole in GCF for each dog ranged from 6.05 to 9.32 αg/mL at different time points after the first dose, and on the first day the highest concentration was observed 6 h after the drug administration. Tinidazole concentrations were 34 ± 4%‐72 ± 9% (mean ± SEM) of simultaneous plasma concentration. At steady‐state, on the third treatment day, the mean tinidazole concentrations in GCF ranged from 6.68 to 13.1 μg/mL, i.e. 44 ± 6%‐75 ± 25% of the corresponding concentrations in plasma. Tinidazole concentration in GCF exceeded the MIC values for putative path‐ogenic periodontal bacteria and it is concluded that, when indicated, tinidazole could be used for chemotherapy of periodontitis in dogs.
Bioavailability of oxytetracycline, tetracycline and chlortetracycline after oral administration to fed and fasted pigs
Authors: NIELSEN P. , GYRD‐HANSEN N.
Published: April 2008

The disposition of oxytetracycline (OTC), tetracycline (TC) and chlortetracycline (CTC) was measured after intravenous and oral administration to pigs. Eighteen healthy pigs (six for each compound) weighing 22‐43 kg received a dose of 10 mg/kg intravenously, and 45 mg/kg (OTC and TC) or 40 mg/kg (CTC) orally in both a fasted and a fed condition in a three‐way crossover design. The three tetracyclines were present in plasma up to 30 hours after intravenous and after oral administration to fasted as well as fed pigs. The volume of distribution was 1.4, 1.2 and 0.7 L/kg body weight for OTC, TC and CTC respectively. The bioavailability was in general low for all the three tetracyclines. The presence of food did not affect the bioavailability of OTC, which was only 3% in both fasted and fed pigs. For TC there was a significantly higher bioavailability in fasted (18%) than in fed (5%) pigs, whereas for CTC the difference was not significant, being 11% in fasted vs. 6% in fed pigs. Even though the presence of food affected the bioavailability only for TC, it prolonged the absorption phase for all three tetracyclines. Based on the bioavailability and the resulting plasma concentrations, it is concluded that it is not possible to obtain a therapeutically active concentration in plasma or tissues after oral administration of any of the three tetracyclines to fed or fasted pigs.
Bioavailability in the rabbit of penicillin and dihydrostreptomycin from three commercial penicillin/aminoglycoside fixed combination products for intramuscular injection
Authors: GROEN K. , FAUW D.P.K.H. PEREBOOM‐DE , van VEEN‐RUTGERS A. , VULTO A. G. , de NEELING A. J.
Published: April 2008

The bioavailability of penicillin and dihydrostreptomycin from three penicillin/ aminoglycoside fixed combination products for intramuscular injection was investigated in a four‐way, randomized, crossover experiment in rabbits. Attention is focused on bioequivalence based on plasma concentration vs. time profiles to study whether the rabbit is a good model to detect differences in in vivo delivery of penicillin and/or dihydrostreptomycin after intramuscular administration of different products. In all products, penicillin was present as a suspension. Although the extent of absorption of penicillin did not differ between the three products, large differences in the rates of absorption were observed. With respect to dihydrostreptomycin, no significant differences were observed between the products. The results from this study demonstrate that the rabbit is a good model to detect differences in bioavailability of suspended penicillin from penicillin/dihydrostreptomycin fixed combination products for intramuscular injection. A study with the same products is presently being carried out in calves to investigate whether bioequivalence studies in rabbits could replace studies in the target animals.
Fenbendazole‐related drug residues in milk from treated dairy cows
Authors: KAPPEL L. C. , BARKER S. A.
Published: April 2008

Oral administration of [14C] fenbendazole (FBZ) at a dose of 5.Omg/kg leads to the presence of radiolabel in the milk of lactating dairy cows. However, the maximum mean concentration of total FBZ equivalents quantitated to one‐third of the recommended safe concentration in milk (1.67 μg/mL). The label is equally distributed to the fat and aqueous portions of the milk. The maximum level, in general, is attained approximately 24‐36 h after drug administration, with the highest levels ranging from 24 to 48 h after administration. The residues rapidly deplete, attaining levels of 10‐20ng/mL by day 5, and are essentially undetectable by radiolabel monitoring by day 6. Extraction of the milk by matrix solid phase dispersion indicated that the label was distributed between traces of the parent drug, FBZ, and predominantly, the FBZ sulphoxide (SO) and sulphone (SO2) metabolites. No other radiolabelled peaks were observed. Based on these data the metabolites of FBZ, FBZ‐sulphone and FBZ‐sulphoxide, could be used as marker residues for monitoring the administration of FBZ to lactating dairy cows.
A study of the pharmacokinetics and tissue residues of an oral trimethoprim/sulphadiazine formulation in healthy pigs
Authors: GARWACKI S. , LEWICKI J. , WIECHETEK M. , GRYS S. , RUTKOWSKI J. , ZAREMBA M.
Published: April 2008

Twenty‐six healthy female pigs weighing 19.5‐33 kg were used in three separate experiments. The animals were fed individually twice a day. Trimethoprim/sulphadiazine (TMP/SDZ) formulation was added to feed in the amount of 6 mg/kg bw (TMP) and 30 mg/kg bw (SDZ). TMP and SDZ concentrations in blood plasma, muscles, liver and kidneys were measured. Pharmacokinetic parameters show that the absorption of TMP from the alimentary tract in pigs is faster than the absorption of SDZ, and the elimination of TMP is slower than that of SDZ. The absorption half‐lives were 0.96 (TMP) and 2.24 h (SDZ), whereas elimination half‐lives were 5.49 (TMP) and 4.19 h (SDZ). The observed TMP:SDZ ratios in blood plasma after multiple dose administration ranged from 1:11.4 to 1:23.2. One day after administration of the last dose of TMP/SDZ the plasma concentration ratio was 1:15.5, but in muscles, liver and kidneys it was much lower: 1:0.79, 1:0.14 and 1:1.53 respectively. The absolute TMP and SDZ tissue concentrations 1 day after the last multiple dose administration were very low (maximum TMP: 0.29 μg/g in liver; maximum SDZ: 0.23 μg/g in kidneys). Neither drug was detected in any tissue 8 days after the last administration of TMP/SDZ. Based on our results, it was concluded that there is no support for the TMP:SDZ pharmaceutical ratio 1:5 in oral formulations of these compounds for pigs. The administration of oral TMP/SDZ formulations once a day may result in the absolute tissue concentrations of these drugs being too low for antibacterial activity. The withdrawal period for such an oral TMP/SDZ formulation for pigs (according to accepted guidelines in Europe for MRL of TMP < 0.05 mg/kg of tissue) should not be less than 5 days.
Clinical efficacy of ampicillin, pivampicillin and procaine penicillin G in a soft tissue infection model in ponies
Authors: ENSINK J. M. , KLEIN W. R. , BARNEVELD A. , VULTO A. G. , van MIERT A.S.J.P.A.M.
Published: April 2008

Tissue chambers, implanted subcutaneously in ponies, were inoculated with Streptococcus zooepidemicus. The animals received either no antibiotics or one of the following treatments: pivampicillin per os (19.9 mg/kg, equivalent to 15 mg/kg ampicillin, every 12 h) for 7 or 21 days (7 and 5 ponies, respectively), procaine penicillin G intramuscularly (12 mg/kg = 12,000 IU/kg, every 24 h) for 7 days (7 ponies), or ampicillin sodium intravenously (equivalent to 15 mg/kg ampicillin, every 8 h) for 1 day (5 ponies). Only intravenous administration was started before infection (prophylactically), the other treatments were started 20 h after infection (curatively). A total of 7 ponies received no antibiotics. In untreated controls, the infection led to abscessation of the tissue chamber in 4 to 10 days. Curative treatment with either pivampicillin or procaine penicillin G for 7 days resulted in a reduction of viable bacteria in the tissue chamber but did not eliminate the infection, resulting in abscessation in 5 to 14 days. However, administration of pivampicillin for 21 days eliminated the streptococci in five out of five ponies and prophylactic administration of ampicillin was successful in three out of five ponies.
Evaluation of the dorsal aorta cannulation technique for pharmacokinetic studies in Atlantic salmon (Salmo salar) in sea water
Authors: SOHLBERG S. , MARTINSEN B. , HORSBERG T. E. , SØLI N. E.
Published: April 2008

The antimicrobial drug flumequine was given intravascularly and orally to cannulated and non‐cannulated Atlantic salmon (Salmo salar) in sea water at 11°. 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 noncannulated 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.
Comparison of urinary and plasma cotinine levels during the three trimesters of pregnancy
Authors: Wu Fang Y. , Chiu Hsien T. , Wu Hong D. Isaac , Lin Chouh J. , Lai Jim S. , Kuo Hsien‐Wen
Published: April 2008

Assays of metabolised cotinine are considered to be an accurate measure of exposure to cigarette smoke among pregnant women. We investigated the association and differences between the cotinine levels in maternal urine and blood, and the umbilical cord blood of three tobacco exposure groups at different stages of pregnancy. A prospective study was conducted among 398 pregnant women undergoing prenatal care in different trimesters at two medical centres and one regional hospital in central Taiwan. All 398 subjects (including 25 smokers, 191 passive smokers and 182 non‐smokers) remained in the study up to the time of delivery; 384 of them delivered singleton live births. Cotinine levels were assayed in the maternal plasma and urine of the mothers at each trimester and in the cord blood of the newborns. All specimens were measured using a sensitive high‐performance liquid chromatography.

Cotinine concentrations in plasma and urine showed a significant dose‐dependent difference among the three groups (non‐smoker, passive and active smoker) and a trend that increased with gestation among the pregnant women. Significant correlations between cotinine concentrations in plasma and urine among the pregnant women in each trimester were found. In addition, the level of cotinine in umbilical cord blood was significantly correlated with that in maternal blood at term (r = 0.89, P < 0.001). A pattern of elevated cotinine concentrations in the plasma and urine of pregnant women from the beginning to the end of pregnancy was found, and this correlated significantly with the cotinine levels in the umbilical cord blood.
Prenatal polychlorinated biphenyl exposures in eastern Slovakia modify effects of social factors on birthweight
Authors: Sonneborn Dean , Park Hye‐Youn , Petrik Jan , Kocan Anton , Palkovicova Lubica , Trnovec Tomas , Nguyen Danh , Hertz‐Picciotto Irva
Published: April 2008

Polychlorinated biphenyls (PCB) were widely used for industrial purposes and consumer products, but because of their toxicity, production was banned by most industrialised countries in the late 1970s. In eastern Slovakia, they were produced until 1985. During 2002–04, a birth cohort of mothers (n = 1057) residing in two Slovak districts was enrolled at delivery, and their specimens and information were collected after birth. Congeners of PCBs were measured in maternal serum by high‐resolution gas chromatography with electron capture detection. In this study, we used multiple linear regression to examine the effects of prenatal PCB exposure on birthweight adjusted for gestational age, controlling for inter‐pregnancy interval, and maternal smoking, age, education, ethnicity, pre‐pregnancy body mass index and height.

The association between total maternal serum PCB levels and birthweight was not statistically significant. However, an interaction model indicated that maternal PCB concentrations were associated with lower birthweight in Romani boys. Based on the fitted regression model, the predicted birthweight of Romani boys at the 90th percentile of maternal PCBs (12.8 ng/mL) was 133 g lower than the predicted birthweight at the 10th percentile of maternal PCBs (1.6 ng/mL). This is a similar magnitude of effect to that observed for maternal smoking and birthweight. These results suggest that higher levels of PCBs in maternal blood sera may inhibit growth in boys, particularly in those already affected by social factors related to ethnicity. This study is consistent with previous findings that boys are more susceptible than girls to growth restriction induced by in utero organochlorine exposures, and further indicates that high PCBs may magnify the influence of social disadvantage in this vulnerable group of boys.
Overexpression of Arabidopsis thaliana tryptophan synthase beta 1 (AtTSB1) in Arabidopsis and tomato confers tolerance to cadmium stress
Authors: SANJAYA  , HSIAO PAO‐YUAN , SU RUEY‐CHIH , KO SWEE‐SUAK , TONG CHII‐GONG , YANG RAY‐YU , CHAN MING‐TSAIR
Published: April 2008

Tryptophan (Trp) is an essential amino acid in humans, and in plants, it plays a major role in the regulation of plant development and defence responses. However, little is known about Trp‐mediated cadmium (Cd) tolerance. Gene expression analysis showed that Arabidopsis thaliana tryptophan synthase beta 1 (AtTSB1) is up‐regulated in plants treated with Cd; hence, we investigated whether this gene is involved in Cd tolerance. Exogenous application of Trp to wild‐type Arabidopsis enhances Cd tolerance. Cd tolerance in the Trp‐overproducing mutant trp5‐1 was associated with high chlorophyll levels and low lipid peroxidation, as indicated by malondialdehyde 4‐hydroxyalkenal level, whereas the wild‐type developed symptoms of severe chlorosis. Moreover, the Trp‐auxotroph mutant trp2‐1 was sensitive to Cd. CaMV 35S promoter‐driven AtTSB1 enhanced Trp accumulation and improved Cd tolerance in transgenic Arabidopsis and tomato plants without increasing the level of Cd. Moreover, reverse transcription‐polymerase chain reaction confirmed that enhanced level of Trp in AtTSB1 transgenic Arabidopsis plants affected the expression of AtZIP4 and AtZIP9 metal transporters, which interfered with Cd ion trafficking, a mechanism of transcriptional regulation that does not exist in wild‐type plants. Overexpression of AtTSB1 in transgenic tomato also produced higher Trp synthase‐β enzyme activity than that in wild‐type plants. These results implicate that Trp could be involved in Cd defence.
Acremonium spp. peritonitis in an infant
Authors: Kendirli Tanıl , Çiftçi Ergin , Ekim Mesiha , Galip Nilüfer , Düzenli Filiz , Özçakar Zeynep Birsin , Tapısız Anıl , Uçar Tayfun , Tutar Ercan , Güriz Haluk , Atalay Semra
Published: April 2008

Fungal peritonitis is a rare but serious complication in children on peritoneal dialysis. Clinical presentation of fungal peritonitis is similar to bacterial peritonitis and Candida spp. are the most common agent. Fungal peritonitis has been usually associated with high morbidity, mortality and its treatment is difficult. In this report, we present an infant with Acremonium spp. peritonitis. A 7‐month‐old boy with Down syndrome, congenital heart disease, pulmonary hypertension and congestive heart failure required peritoneal dialysis for his persistent pulmonary oedema and symptomatic hyponatremia. Acremonium spp. peritonitis developed while he was on extended spectrum antibiotics and fluconazole. The patient was successfully treated with peritoneal dialysis catheter removal and liposomal amphotericin B. The case was presented to draw attention to a rare cause of peritonitis –Acremonium spp. – in a paediatric patient.
Research assessment of elder neglect and its risk factors in a hospital setting
Authors: Cohen M.
Published: April 2008

Background:  The aims of this experiment were to assess the rate of neglect in hospitalized patients and to identify risk factors for neglect.

Methods:  During 2004–2006, patients aged 70 years and older hospitalized in internal departments were screened for signs of neglect. Principal caregivers were interviewed too.

Results:  Signs of neglect were identified in 14.1% of the patients. Neglected patients differed from the non‐neglected in level of education and had poorer economic status and more frailty, lower albumin level, higher incontinence problem and higher subjective caregiving burden reported by their caregivers. Mean risk scores, based on patients’ and caregivers’ risk indicators, were higher in the neglect group.

Conclusion:  Health, functional and psychosocial factors correlated to the presence of neglect. These factors should be used as warning signs to draw attention to professional help.