bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of age and diet on sulfadiazine/trimethoprim disposition following oral and subcutaneous administration to calves
Authors: SHOAF S. E. , SCHWARK W. S. , GUARD C. L. 
Published: April 2008

Shoaf, S.E., Schwark, W.S. & Guard, C.L. The effect of age and diet on sulfadiazine/trimethoprim disposition following oral and subcutaneous administration to calves. J. vet. Pharmacol. Therap. 10, 331–345.Thirty milligrams per kilogram of sulfadiazine/trimethoprim (SDZ/TMP, Trib‐rissen®) was given orally and subcutaneously (s.c.) to two groups of male, Hol‐stein calves. One group was fed milk‐replacer throughout the 13‐week period of the study while the second group was weaned onto a chopped grain‐fiber mixture when 5 weeks old. Serum and urine were assayed for concentrations of unchanged drug. Trimethoprim bioavailability, following oral administration at 1, 6 and 12 weeks of age, is higher in milk‐fed calves (non‐ruminants) than in grain‐fiber‐fed calves (ruminants); bioavailability decreases with increasing age in both groups of calves. Serum concentrations above 0.1 μg/ml (the level of sensitivity of the assay) could not be obtained in ruminating calves. The rate of SDZ absorption following oral administration, as determined by the Wagner‐Nelson method, was very slow in all the calves in this study with average half‐life values ranging from 8.2–12.67 h; absorption was slightly faster in ruminating calves. Absorption of SDZ is rate‐limiting and determines the biological half‐life of the drug; SDZ serum concentrations above 2 (μg/ml were maintained in all calves for at least 24 h. Following s.c. administration of Tribrissen®to 7‐and 13‐week‐old calves, urinary excretion patterns indicated that TMP was slowly released from the injection site; serum concentrations were below 0.1 μg/ml. In contrast, absorption of SDZ was very rapid; values for tmax were 1.5–1.8 h. The pharmacokinetic parameters for SDZ were calculated according to a one‐compartment open model; neither diet nor age had a significant effect on SDZ disposition following s.c. injection. Subcutaneous administration of 30 mg/kg Tribrissen®, b.i.d., may be the best therapeutic regimen; even though measure‐able concentrations of TMP cannot be achieved in the serum following a single s.c. dose, TMP concentrations should accumulate and, because of its sustained release, provide almost continual potentiation of SDZ.
Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs
Authors: LABER G. 
Published: April 2008

Laber, G. Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs. J. vet. Pharmacol. Therap.11, 45–49.Kinetic variables for tiamulin in the normal dog have been determined. Serum concentrations of tiamulin were compared after intramuscular (i.m.) and subcutaneous (s.c.) administration of a single dose of tiamulin. Following a single i.m. dose of 10 mg/kg body weight, the compound was calculated to have a Cmax= 0.61 ± 0.15 μg/ml, a Tmax= 6 h and a t½= 4.7 ± 1.4 h. Tiamulin showed dose‐dependent pharmacokinetics when given as a single s.c. dose of either 10 mg or 25 mg/kg body weight. For the lower dose, the values Cmax= 1.55 ± 0.11 μg/ml, Tmax= 8 h and 1max= 4.28 ± 0.18 h were obtained. For the higher dose Cmax= 3.14 ± 0.04 μg/ml, Tmax= 8 h and t½= 12.4 ± 3.4 h were calculated. When tiamulin was administered subcutaneously at a dose rate of 10 mg/kg body weight, higher and better maintained serum levels were achieved than those following i.m. administration. After repeated s.c. doses no significant accumulation of tiamulin occurred. Assuming that a continuous effective serum concentration is necessary throughout the course of therapy, these data would indicate that tiamulin should be given every 24 h.
The oxidative metabolism of fenbendazole: a comparative study
Authors: SHORT C. R. , FLORY W. , HSIEH L. C. , BARKER S. A. 
Published: April 2008

Short, C.R., Flory, W., Hsieh, L.C. & Barker, S.A. The oxidative metabolism of fenbendazole: a comparative study. J, vet. Pharmacol. Therap. 11, 50–55.The oxidative metabolism of fenbendazole (FBZ) was studied in hepatic fractions prepared from livers of cattle, sheep, goats, chickens, ducks, turkeys, rats, rabbits and catfish. All species produced the sulfoxide metabolite (oxfendazole; FBZ‐SO), and p‐hydroxyfenbendazole (FBZ‐OH) was produced by all species except sheep. The product of demethoxycarbonylation, fenbendazole amine (FBZ‐NH2), was not produced by liver preparations of any species. A fourth metabolite, resulting from the further oxidation of oxfendazole, fenbendazole sulfone (FBZ‐S02), was formed in all species but at highly varying rates. The chicken exhibited the highest overall rate of FBZ metabolism, followed by the duck, goat, sheep, steer, catfish, rat, rabbit, and turkey. Considerable variation was evident among avian species, the duck and turkey produced substantially less of the FBZ‐OH and FBZ‐SO2 metabolites than the chicken. Catfish liver preparations formed equivalent amounts of metabolite at 25oC and 37oC incubation temperatures. The formation of the sulfone metabolite (FBZ‐SO2), however, was practically nonexistent in catfish.
Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick‐borne fever infected dwarf goats
Authors: KNOPPERT N. W. , NIJMEIJER S. M. , DUIN C. T. M. VAN , KORSTANJE C. , GOGH H. VAN , MIERT A. S.J. P. A. M. VAN 
Published: April 2008

Knoppert, N.W., Nijmeijer, S.M., van Duin, C.T.M., Korstanje, C., van Gogh, H. and van Miert, A.S.J.P.A.M. Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick‐borne fever infected dwarf goats. J. vet. Pharmacol. Therap.11, 135—144.Aditoprim (AP) is a new dihydrofolate reductase inhibitor, which is structurally related to trimethoprim (TMP). The pharmacokinetics of AP (10 mg/kg) and TMP (20 mg/kg) were assessed in healthy dwarf goats. Therapeutic efficacy against rickettsial infections was tested in tick‐borne fever (TBF) infected goats. The animals were given TMP (n = 5) or AP (w = 5) by i.v. injection, and subsequently the drugs were administered orally (same groups, similar doses). Finally, both groups were infected with TBF and the i.v. experiment was repeated. Plasma concentration—time curves for both drugs followed first‐order two‐compartment decay. For TMP, mean t½β± SEM (h) was 0.84 ± 0.06 (i.v. control) and 0.90 ± 0.06 (i.v. infected), respectively, whereas for AP values of 8.00 ± 0.31 (i.v. control) and 10.28 ± 0.67 (i.v. infected) were obtained (P < 0.05). Mean Vdp± SEM values (1/kg) were 3.84 ± 0.27 (i.v. control) and 4.07 ± 0.85 (i.v. infected) for TMP (NS) and 7.02 ± 0.63 vs 9.29 ± 0.21 (P < 0.05) for AP. After i.v. injection, rumen fluid concentrations of AP were significantly (P < 0.05) higher and more persistent than those of TMP. For AP, the plasma and rumen fluid concentrations at 3 h were 1.20 ± 0.06 (Xg/ml and 0.85 ± 0.17 (ig/ml, respectively. After oral administration of TMP, Cmax in plasma was 0.12 ± 0.01 (ig/ml and the maximum was reached after 1.2 ± 0.16 h; systemic bioavailability (F) was 10.3% (relative to AUC i.v.). Oral treatment with AP resulted in a Cmax value of 0.21 ± 0.02 μg/ml with Tmax of 22.5 ± 1.65 h and a F value of 71%. Based on WBC, serum ALP and rectal temperature responses, it was concluded that both TMP and AP were inactive against Ehrlichia phagocytophila.
The pharmacodynamics of ivermectin in sheep and cattle
Authors: BOGAN THE LATE'J. A. , McKELLAR Q. A. 
Published: April 2008

Bogan, J.A. (deceased) & McKellar, Q.A. The pharmacodynamics of ivermectin in sheep and cattle. J. vet. Pharmacol. Therap. 11, 260–268.The concentrations of ivermectin in the gastrointestinal tract of sheep and cattle were determined after subcutaneous administration of ivermectin. Ivermectin was not detected (limit of detection 1 ng/ml) in abomasal and ruminal fluids either after a normal therapeutic dose of 200 μg/kg or even at an increased dose of 2000 μg/kg. It was also not detected in abomasal and ruminal fluids of a sheep infected with the abomasal parasite Osterlagia circumcincta. However, ivermectin was detectable at similar concentrations in abomasal mucus and in small intestinal mucus. Excretion of ivermectin was high in bile but the concentrations in small intestinal mucus, distal and proximal to the bile duct opening, were similar. It is hypothesized that the low efficacy of ivermectin against small intestinal nematodes compared with abomasal nematodes is not due to differences in ivermectin concentrations in the predilection sites but is probably due to tachyphylaxis in the nematodes allowing the small intestinal nematodes to re‐establish before they have left their predilection site. Ivermectin was excreted in the milk of ewes at concentrations similar to those in plasma. Lambs suckling ivermectin‐treated ewes received about 4% of a normal therapeutic dose (200 μg/kg) via the milk.
Actions of the novel gastrointestinal pro kinetic agent cisapride on equine bowel motility
Authors: KING J. N. , GERRING E. L. 
Published: April 2008

King, J.N. & Gerring, E.L. Actions of the novel gastrointestinal prokinetic agent cisapride on equine bowel motility. J. vet. Pharmacol. Therap. 11, 313–321.The effect of cisapride was evaluated on the normal fasting bowel motility of four ponies with chronically implanted electromechanical transducers. Cisapride was infused over 60‐min periods at 0.05 mg/kg (n= 4), 0.1 mg/kg (n= 5) and 0.25 mg/kg (n= 5). It produced marked and prolonged increases in electrical and mechanical activity at all sites examined. In the stomach there was increased total contraction activity with increased contraction amplitude and a slight reduction in rate. In the small intestine there was an increase in irregular (phase II) activity with an increase in number and amplitude of contractions and a decrease in the number of regular (phase III) activity fronts. There was a decrease in the number of phase III fronts that spread distally from the jejunum to the ileum. The phase II activity was coordinated temporally with prolonged activity in the stomach. Cisapride increased electrical and contractile activity in the left dorsal colon with increased contraction amplitude and an increase in electrical activity in the small colon. In the stomach and small intestine cisapride produced dose‐dependent increases in activity but in the left dorsal and small colon the intermediate dose (0.1 mg/kg) produced the largest and most consistent responses. Side‐effects observed were increased bowel sounds and frequency of defaecation, a slight increase in heart rate and transient signs of discomfort at the highest (0.25 mg/kg) dose rate.
Prokinetic effects of cisapride, naloxone and parasympathetic stimulation at the equine ileo‐caeco‐colonic junction
Authors: RUCKEBUSCH Y. , ROGER T. 
Published: April 2008

Ruckebusch, Y. & Roger, T. Prokinetic effects of cisapride, naloxone and parasympathetic stimulation at the equine ileo‐caeco‐colonic junction. J. vet. Pharmacol. Therap.11, 322–329.The electromyogram of the terminal ileum, the caecum and the proximal right ventral colon was recorded in fasted conscious ponies receiving intravenously equiactive doses of pilocarpine (0.05 mg/kg) and carbachol (0.01 mg/kg) as acetylcholine analogues; cisapride (0.1 mg/kg) and metoclopramide (2 mg/kg) facilitating acetylcholine release from myenteric neurones and naloxone (0.05 mg/kg) as an antagonist of the endogenous inhibitory opioid system. Both cisapride and naloxone induced typical migrating spike bursts in the colon associated with contractions of caecal body and caecal base. Both pilocarpine and carbachol stimulated the terminal ileum but had opposite effects on the activity of the caeco‐colonic segment which was decreased by pilocarpine and increased by carbachol. High doses of metoclopramide had weak and unspecific stimulatory motor effects. It is concluded that a true prokinetic effect at the equine ileo‐caeco‐colonic junction requires a motor profile which includes coordination between contractions sequentially involving the body and the base of the caecum and migrating spike bursts on the proximal colon. Such changes in the motor profile were produced by cisapride and naloxone and to a lesser extent by carbachol.
Comparison of serum and renal gentamicin concentrations with fractional urinary excretion tests as indicators of nephrotoxicity
Authors: BROWN S. ANTHONY , GARRY F. B. 
Published: April 2008

Anthony Brown, S., & Garry, F.B. Comparison of serum and renal gentamycin concentrations with fractional urinary excretion tests as indicators of nephrotoxicity. J. vet. Pharmacol. Therap.11, 330–337.Gentamicin was given to six sheep at a dosage rate of 80 mg/kg/day divided into three daily doses to cause nephrotoxicity. Peak serum gentamicin concentrations rose significantly throughout dosing (P < 0.05), but trough serum gentamicin concentrations increased dramatically (P < 0.01) from initial concentrations of 3.2–9.1 μg/ml to final trough concentrations of 31.5–195 μg/ml by 6–10 days on gentamicin. The serum gentamicin elimination half‐life (t1/2) was doubled in each animal by approximately 6 days on therapy, with the sheep that were the most clinically affected by the nephrotoxic effects of gentamicin showing increases in t1/2 earlier than those sheep that remained less intoxicated. These changes occurred before many other clinical indicators of nephrotoxicity, with only urinary enzyme excretions preceding the changes in gentamicin elimination. Thus, alterations in the elimination of gentamicin may be one of the first clinical indicators of the occurrence of gentamicin‐induced nephrotoxicity.
Apomorphine‐induced emesis in the dog‐routes of administration, efficacy and synergism by naloxone
Authors: SCHERKL R. , HASHEM A. , FREY H.‐H. 
Published: April 2008

Scherkl, R., Hashem, A. & Frey, H.‐H. Apomorphine‐induced emesis in the dog‐routes of administration, efficacy and synergism by naloxone. J. vet. Pharmacol. Therap. 13, 154–158.Apomorphine proved to be more effective as an emetic in dogs after s.c. administration than after i.m. injection with doses of 0.04 and 0.1 mg/kg. This effect is explained by an anti‐emetic effect mediated by μ‐receptors in the vomiting centre in die brain, which, in contrast to the chemoreceptor trigger zone, is within the blood‐brain barrier. A certain delay between the stimulation of D2‐receptors in the chemoreceptor trigger zone (causing emesis) and μ‐receptors in the vomiting centre (producing anti‐emesis) therefore results, leading to a self‐limiting emesis. Blockade of the μ‐receptors by naloxone increased and prolonged the effect of apomorphine. A relatively narrow range of apomorphine concentrations on s.c. administration is then effective to stimulate the chemoreceptor trigger zone, but can hardly inhibit the vomiting centre, and must therefore be considered the most suitable route for administration of apomorphine. R. Scherkl, Department of Pharmacology and Toxicology, School of Veterinary Medicine, Free University of Berlin, Koserstr. 20, D‐1000, West Berlin, FRG.
Pharmacokinetics of fenbendazole in dogs
Authors: McKELLAR Q. A. , HARRISON P. , GALBRAITH E. A. , INGLIS H. 
Published: April 2008

McKellar, Q.A., Harrison, P., Galbraith, E.A. & Inglis, H. Pharmacokinetics of fenbendazole in dogs. J. vet. Pharmacol. Therap. 13, 386–392.Fenbendazole was administered to dogs at a dose rate of 20 mg/kg body weight on a single occasion in gelatin capsules, on 5 consecutive days in feed, and on a single occasion as an alginate suspension. It was also administered at a dose rate of 100 mg/kg body weight on a single occasion in feed. Following single administration of 20 mg/kg fenbendazole mean maximum concentrations (Cmax) of the parent drug and its known active sulphoxide metabolite were 0.42 ± 0.05 and 0.31 ± 0.05 μg/ml, respectively. Mean times until maximum concentrations were achieved (tmax) were 12.67 ± 4.18 and 15.33 ± 2.81 h, respectively, and areas under the plasma concentration‐time curves (AUC) were 5.83 ± 0.65 and 4.60 ± 0.57μg.h/ml, respectively. Administration in feed increased the apparent bioavailability and administration for 5 consecutive days provided sustained plasma concentrations, generally > 0.2μg/ml. Administration as an alginate did not increase bioavailability or extend the persistence in plasma. It did increase the tmax to 16.80 ± 2.93 and 20.00 ± 2.53 h for fenbendazole and its sulphoxide metabolite, respectively. Increasing the dose from 20mg/kg to 100mg/kg did not substantially increase the Cmax or AUC. Q. A. McKellar, Department of Veterinary Pharmacology, University of Glasgow Veterinary School, Bearsden Road, Bearsden, Glasgow G61 1QH, UK.
Comparative pharmacokinetics of doxycycline in cats and dogs
Authors: RIOND J.‐L. , VADEN S. L. , RIVIERE J. E. 
Published: April 2008

Riond, J.‐L., Vaden, S.L. & Riviere, J.E. Comparative pharmacokinetics of doxycycline in cats and dogs.J. vet. Pharmacol. Therap.13, 415–424.The disposition of doxycycline hyclate was studied in six adult mixed‐breed female cats and six adult mid‐sized female dogs following a single intravenous administration of 5 mg/kg body weight. Doxycycline volume of the central compartment, area volume of distribution, volume of distribution at steady state, and total body clearance were significantly smaller in cats. The differences were attributed to more extensive binding of doxycycline to plasma protein including albumin in cats. The significant differences in the volume of distribution and total body clearance were not reflected in elimination half‐lives under the conditions of this study (sample size, inhomogeneous population). Doxycycline elimination half‐life was 4.56±0.68 (SEM)h for cats and 6.99±1.09h for dogs. Dosage regimens recommended in the veterinary literature were evaluated by the computer program PETDR.Dr J. E. Riviere, Laboratory of Toxicokinetics, Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina Stale University, Raleigh, NC 27606, USA.
Fever and acute phase response induced in dwarf goats by endotoxin and bovine and human recombinant tumour necrosis factor alpha
Authors: VAN MIEKT A. S. J. P. A. M. , VAN DUIN C. T. M. , WENSING Th. 
Published: April 2008

Tumour necrosis Factor (TNF), a polypeptide produced by mononuclear phagocytes, has been implicated as an important mediator of inflammatory processes and of clinical manifestations in acute infectious diseases. To study further the potential role of TNF in infectious diseases, recombinant Escherichia colt (E. coli) derived human (r.HuTNF‐α) and bovine TNF (r.BoTNF‐α) were intravenously (i.v.) administered in dwarf goats. Rectal temperature, heart rate, rumen motility, plasma zinc and iron concentrations, and certain other blood biochemical and haematological values were studied and conipared with the changes seen after E. coli endotoxin (LPS) was administered (dose: 0.1 μg/kg i.v.). Following a single injection of 4 μg/kg of r‐.BoTNF‐α, shivering and biphasic febrile response were observed, accompanied by tachycardia, inhibition of rumen contractions, drop in plasma zinc and iron concentrations, lynipho‐penia, and neutropenia Followed by neutrophilia. The i.v. administration of a single injection of 4 μg/kg r.HuTNF‐α induced shivering and biphasic febrile responses, accompanied by anorexia and a similar drop in plasml trace metal concentrations when compared with r.BoTNF‐α‐treated goats. The TNF‐α‐induced symptoms were essentially the same as those that occurred after LPS administration. However, the time of onset of these changes after the injection of TNF‐a was significantly shorter than after LPS. Moreover, the r.BoTNF‐α induced a longer lasting neutrophilic leucopenia, less neutrophilia, and a more persistent lymphopenia than after LPS injection. Neither r.BoTNF‐α nor LPS caused severe haemo‐concentration. Furthermore, no cross‐tolerance between r.BoTNF‐α and LPS could be demonstrated.We conclude that both r.BoTNF‐α and r.HuTNF‐α induce many of the physiologic, haemacologic and metabolic changes that characterize the acute phase response to LPS. The overlapping biological activities of r.‐BoTNF‐α, r.HuTNF‐α and LPS in dwarf goats may indicate that both recombinant tumour necrosis factors have some homology with caprine TNF‐α.
Pharmacokinetics of midazolam administered concurrently with ketamine after intravenous bolus or infusion in dogs
Authors: BROWN S. A. , D.JACOBSON J. , HARTSFIELD S. M. 
Published: April 2008

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 t½α of 1.8 min and t½β.p of 27.8 min after i.v. bolus, and t½α f 1–35 min and t½β 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 ClB 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.
A comparison of the actions of platelet activating factor (PAF) antagonists WEB 2170 and WEB 2086 in the horse
Authors: FOSTER A. P. , CUNNINGHAM F. M. , ANDREWS M.J. , LEES P. 
Published: April 2008

Foster, A.P., Cunningham, F.M., Andrews, M.J., Lees, P. A comparison of platelet activating factor (PAF) antagonists WEB 2170 and WEB 2086 in the horse. J. vet. Pharmacol. Therap. 16, 477–487.The effects of the selective platelet activating factor (PAF) receptor antagonist WEB 2170 on PAF‐induced responses in equine cells and tissues have been examined and compared with those of WEB 2086. In initial experiments WEB 2170 was shown to inhibit in vitro platelet aggregation in a dose‐dependent, competitive reversible manner (pA2= 7.21). Co‐administration of the antagonists with either PAF or histamine also inhibited PAF, but not histamine, induced wheal formation and PAF‐induced neutrophil accumulation in vivo in equine skin. Intravenous (i.v.) administration of both drugs at a dose of 0.1 mg/kg blocked PAF‐induced ex vivo platelet aggregation. The inhibition produced by WEB 2170 was greater and, at 30 min, this drug also reduced the slope and maximal response. Wheal formation in the skin was significantly inhibited for up to 6 h by WEB 2170 administered i.v., the reduction being more prolonged than that obtained with WEB 2086. Neutrophil accumulation in the skin was also significantly reduced for up to 24 h by WEB 2170, whilst no significant inhibition was produced by WEB 2086. These results demonstrate that WEB 2170, like WEB 2086, is an effective antagonist of PAF in the horse. Moreover, when given i.v., WEB 2170 appears to be a more potent PAF inhibitor than WEB 2086.