bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mode of action of common anthelmintics
Authors: REW ROBERT S. 
Published: April 2008

The primary physiological mode of action of nearly all drugs used to control helminth parasites is not well understood. Examination of the general modes of action in terms of parasite requirements for survival may, however, provide guidelines to continue our present investigations and direct us for future research.Two general areas of drug activity are (1) interference with energy‐generating metabolism, and (2) interference with proper neuromuscular coordination. Few exceptions are found to these areas because the target organisms require little else for survival.The target of most previously effective and many presently effective anthelmintics is an adult parasite. Adult helminth parasites must maintain an advantageous feeding site and must transport and metabolize substrates (primarily glucose) to generate life‐maintaining energy. Adult worms have almost no other short‐term requirements for survival because they have little or no metabolic activity in either lipid synthesis or oxidation, nucleic acid synthesis, or protein synthesis (except egg‐laying).Examination of specifics of energy‐generating metabolism and putative neurochemical transmitters allows us certain predictions in relating a given drug activity to an individual species. These examinations indicate that such diversity exists among helminth metabolic or nervous systems that a broad‐spectrum anthelmintic would most likely inhibit at several sensitive points.Published information on drug action and differences in data interpretation are discussed. Two novel areas for future anthelmintic investigations may be (1) juvenile hormone or ecdysone analogs, and (2) pheromones. A combined empirical and rational approach to the development of new drugs may be the most efficient avenue of future research.
Evaluation of a new treatment for canine scabies and demodicosis
Authors: FOLZ S.D. , GENG S. , NOWAKOWSKI L.H. , CONKLIN R.D. 
Published: April 2008

A total of forty‐eight dogs were utilized to titrate and evaluate the activity of a new miticide, amitraz. The treatment was applied dermally and evaluated for efficacy against experimentally induced Demodex canis and Sarcoptes scabiei infestations. Five different concentrations (2000, 1000, 500, 250, 125 p.p.m.) of the active drug, N'—(2, 4‐dimethylphenyl)N—{[(2, 4‐dimethylphenyl) imino] methyl} ‐N‐methyl‐methanimidamide, were tested. The activity of amitraz was compared to a standard treatment, placebo treatment, and no treatment.A single dermal treatment with amitraz (all concentrations) indicated activity against both D. canis and S. scabiei. The lowest concentration of active drug (125 p.p.m.) was significantly less efficacious than the four higher concentrations (250, 500, 1000, 2000 p.p.m.). At the 250 p.p.m. (or higher) level the effectiveness of this new miticide was comparable to the standard treatment. The data indicate the 250 p.p.m. concentration is the optimal level and the recommended dilution for treatment of mange mites. Drug reactions related to amitraz were not observed.
Serum digoxin concentrations in dogs before and during concomitant administration of furosemide
Authors: PEDERSOLI W. M. , NACHREINER R. F. 
Published: April 2008

Healthy dogs were treated once a day for 16 days with a liquid, oral dosage form of digoxin (0.022 mg/kg). From day 9 to 16 they were also injected intramuscularly with furosemide (4.4 mg/kg). Serum digoxin was measured by a radioimmunoassay technique. Eight hours after the eighth dose of digoxin had been administered, serum digoxin concentration was in the accepted therapeutic range. After 8 days of concomitant administration of digoxin and furosemide, serum digoxin concentration was found to be in the accepted moderate‐to‐severe toxic range. Clinical signs of digitalis toxicosis were consistently observed during the combined digoxin‐plus‐furosemide treatment period. There was no significant (P>0.05) change in the serum concentrations of potassium, sodium, or in osmolality during digoxin treatment alone. Serum creatinine concentrations remained within the accepted normal range for dogs. Serum sodium concentration was significantly (P<0.05) lower during combined digoxin‐plus‐furosemide treatment when compared to digoxin treatment only.Results indicate that an interaction between digoxin and furosemide occurred which led to significantly (P<0.05) higher concentrations of serum digoxin during combined digoxin and furosemide treatment.
Pharmacokinetic studies of theophylline in dogs
Authors: McKIERNAN B. C. , NEFF‐DAVIS C. A. , KORITZ G. D. , DAVIS L. E. , PHERIS D. R. 
Published: April 2008

The pharmacokinetics of theophylline were investigated in dogs following intravenous, single oral, and multiple oral doses of aminophylline. Mean half‐life (t1/2) of theophylline following single intravenous administration was 5.7 h and the apparent specific volume of distribution (V'd area) was 0.82 litre/kg. The bioavailability of theophylline was high (91%) following oral administration of aminophylline tablets and the absorption half‐life (t1/2 ab) was 0.4 h.Theophylline plasma concentrations observed following repeated oral administration of aminophylline tablets were somewhat greater than predicted. This suggests that theophylline plasma concentrations should be monitored and the dosage regimen individually adjusted in critically ill animals.
Fenbendazole and thiabendazole in cattle: partition of gastrointestinal absorption and pharmacokinetic behaviour
Authors: PRICHARD R. K. , STEEL J. W. , HENNESSY D. R. 
Published: April 2008

Fenbendazole (FBZ) and thiabendazole (TBZ) were administered intraruminally with a single dose of an indigestible marker, chromium ethylenediaminetetra‐acetate (Cr‐EDTA), to cattle fitted with gastrointestinal cannulae. The amounts of anthelmintic leaving the rumen, abomasum and terminal ileum in digest a were derived by compartmental analysis of Cr‐EDTA concentrations and integration of benzimidazole concentrations.TBZ was absorbed much more rapidly from the rumen than FBZ and only about 12% of the dose left the rumen in digesta compared with 30% of the FBZ. Approximately 10% and 8% of the TBZ dose appeared at the pylorus and terminal ileum, respectively. Of the above amounts, 9% in the abomasum and practically 100% in the ileum was present as 5‐OH‐TBZ, indicating that metabolites of absorbed TBZ were recycled to the gastrointestinal tract. Twenty‐eight percent and 52% of the FBZ appeared at the pylorus and terminal ileum, respectively, indicating a substantial recycling of absorbed drug to the small intestine. It is suggested that biliary secretion of both TBZ and FBZ and their metabolites may contribute to this recycling.Maximal concentrations of TBZ occurred in plasma in 4 h compared with about 24 h for FBZ. TBZ and metabolites were excreted in urine much more rapidly than were FBZ and metabolites. In plasma and in each of the gastrointestinal compartments, FBZ persisted much longer than did TBZ. It was concluded that slower absorption and excretion and more extensive recycling to the gastrointestinal tract of FBZ, than of TBZ, contribute markedly to its greater potency against helminths.
Dexamethasone in cattle: pharmacokinetics and action on the adrenal gland
Authors: TOUTAIN P. L. , BRANDON R. A. , ALVINERIE M. , GARCIA‐VILLAR R. , RUCKEBUSCH Y. 
Published: April 2008

The pharmacokinetics of Dexamethasone (DXM) was studied in four cows all of which received DXM alcohol and DXM 21 isonicotinate (as a solution) by the intravenous and intramuscular routes. Concentrations of DXM and cortisol were determined using high performance liquid chromatography. An additional study was made in a second group of four cows which received intramuscular DXM 21 isonicotinate suspension for the assessment of DXM suppression of adrenal gland function. This was determined by measurements of base‐line and ACTH‐stimulated cortisol concentrations, before and following DXM administration.Following intravenous administration, the disposition kinetics of both formulations were described by a two‐compartment open model. The half‐times of elimination were similar; 335 and 291 min, respectively, for DXM alcohol and DXM 21 isonicotinate. All other pharmacokinetic parameters were not statistically different indicating that DXM was almost totally available (from DXM 21 isonicotinate). Following intramuscular administration, no significant difference in parameters was observed between the two formulations. Peak plasma concentrations were reached at 3 to 4 h post injection and bioavailability was approximately 70%. DXM was not detected in the plasma after the intramuscular administration of the suspension.The mean control plasma cortisol concentration was 8.8 ± 3.03 ng/ml. Following intravenous and intramuscular administrations of DXM alcohol and DXM 21 isonicotinate (solution), cortisol concentrations initially increased. However, at 120 min (intravenous) and 2–4 h (intramuscular), concentrations were negligible; 24–72 h and 48–96 h, respectively elapsed before concentrations returned control values. Following DXM 21 isonicotinate (suspension) there was no initial increase and concentrations had not returned to normal in all four cows until 52 days post administration. Similarly, ACTH‐stimulated plasma cortisol concentrations decreased progressively and significantly post administration. At 52 days, response to ACTH was normal in all animals.
Pharmacokinetics of chloramphenicol in non‐lactating cattle
Authors: ANDERSON K. L. , NEFF‐DAVIS C. A. , DAVIS L. E. , KORITZ G. D. , NELSON D. R. 
Published: April 2008

The pharmacokinetics and bioavailability of a formulation of chloramphenicol base in propylene glycol were determined following administration of single intravenous (i.v.) and subcutaneous (s.c.) 50 mg/kg doses of chloramphenicol to six non‐lactating Holstein cows.Mean serum concentrations of chloramphenicol following i.v. administration of 50 mg/kg declined rapidly from a peak of greater than 100 μg/ml to 6.9 μg /ml at 12 h after administration.Serum concentrations were not detectable at 24 h after administration. The curve of serum concentrations vs time was characteristic of a two‐compartment open model. Mean i.v. data gave a biological half‐life of 4.3 h and a volume of distribution of the central compartment of 0.44 1/kg. Serum concentrations of chloramphenicol following s.c. administration of 50 mg/kg rose slowly to a broad peak near 20 μ g/ml from 3 to 8 h after administration and then declined. These data were also analysed according to a two‐compartment open model. The biological half‐life was 4.2 h and the volume of distribution of the central compartment was 0.50 1/kg.Significant adverse reactions, including acute collapse, intravascular haemolysis and haemoglobinuria, were observed in cows when dosed i.v. Cows dosed s.c. exhibited local reactions at injection sites.The disadvantages of administration of 50 mg/kg doses of chloramphenicol base in propylene glycol appear to be significant and may outweigh the potential advantages of parenteral use of the drug as presently formulated.
Pharmacokinetics of chloramphenicol in the neonatal horse
Authors: BRUMBAUGH GORDON W. , MARTENS RONALD J. , KNIGHT HUMPHREY D. , MARTIN MICHAEL T. 
Published: April 2008

Chloramphenicol sodium succinate was administered as an intravenous bolus (50 mg/kg) to eight foals which weighed 49–57 kg (mean ± 1 standard deviation = 53.19 ± 2.66) each, and were 1–9 days (4.5 ± 2.56) of age. The drug was rapidly distributed and followed first‐order elimination. Mean pharmacokinetic values were: zero‐time serum concentration (C0) = 36.14 μg/ml (±14.80); apparent specific volume of distribution (Vd) = 1.614 1/kg (±0.669); and elimination rate constant (K) = 0.7295 h‐1 (±0.3066) which corresponds to a biological half‐life (t1/2) = 0.95 h. These values do not differ greatly from those reported for adult horses and ponies.A suspension of chloramphenicol was administered by nasogastric tube (50 mg/kg) to a second group of seven foals which weighed 49 to 57 kg (51.34 ± 2.82) each and were 1 to 7 days (4.43 ± 1.90) of age. A mean peak serum chloramphenicol concentration of 23.97 μg/ml (±7.06) was achieved 1.14h (±0.63) after administration. The bioavailability of this preparation was 83.27 percent.
Treatment of Moraxella bovis infections in calves using a long‐acting oxytetracycline formulation
Authors: GEORGE LISLE W. , SMITH J. A. 
Published: April 2008

George, L.W. & Smith J.A. Treatment of Moraxella bovis infections in calves using a long‐acting oxytetracycline formulation. J. vet. Pharmacol. Therap. 8, 55–61.Studies were undertaken to determine the effectiveness of an oxytetracycline HCl formulation for the prophylaxis and treatment of chronic Moraxella bovis ocular infections in calves. Two separate experiments were performed. For the first, calves were separated into two groups and the eyes were infected with M. bovis. The eyes of these calves were observed and cultured for 37 consecutive days. On the 37th and 40th day, each of the five calves were treated intramuscularly with the drug (20 mg/kg of body weight). The other five calves (second group) remained untreated as controls. The cultures from the five treated calves were negative after the first antibiotic administration and remained so for 14 days. M. bovis was isolated from each eye of the control calves at least once during that time. None of the antibiotic‐treated calves was completely resistant when reinfected with M. bovis. For the second experiment, calves were given a prophylactic administration of the formulation and were then infected with M. bovis 48 (n= 4 calves) or 72 (n= 4 calves) h later. These treatments resulted in a lower incidence of keratoconjunctivitis and a decreased duration of bacterial shedding, as compared to controls (n= 8 calves), but did not completely prevent the occurrence of disease or the establishment of ocular infections. Lisle W. George, Department of Medicine, School of Veterinary Medicine, University of California, Davis, CA 95616, U.S.A.
Clinical pharmacology of apramycin in calves
Authors: ZIV G. , BOR A. , SOBAGK S. , ELAD D. , NOUWS J. F. M. 
Published: April 2008

Ziv, G., Bor, A., Sohack, S., Elad, D. & Nouws, J.F.M. Clinical pharmacology of apramycin in calves. J. vet. Pharmacol. Therap. 8, 95–104.The minimal inhibitory concentrations (MIC) of apramycin, a unique aminocy‐clitol antibiotic, were compared with the MIC of dihydrostreplomycin and neomycin for 323 Salmonella, 178 Escherichia coli and twenty‐six Pasteurella multocida isolates recovered from newborn calves. Apramycin exhibited better in vitro anti‐bacterial activity than dihydrostreptomycin and neomycin; isolates of Salmonella group B and E. coli resistant to the latter were sensitive to apramycin.The durations of free drug concentrations in the tissues after i.v. and i.m. injection were estimated from the serum drug level data, percent of serum protein binding, Vdss, 1/2ß and the MIC. Computations showed that apramycin should be administered i.m. at 20 mg/kg every 24 h in order to maintain in tissues potentially effective drug concentrations sufficient to inhibit 50% of the Salmonella, E. coli, and P. inullocida isolates, and at 12‐h intervals to inhibit 90% of the isolates. G. Ziv, Ministry of Agriculture, Kimron Veterinary Institute, P.O. Box 12, Bet Dagan, Israel.
The effect of intermittent treatment with sulphadimidine on coccidiosis in preruminant calves
Authors: ĈELEDA L. , URBANOVÁ Z. , PAVLÁSEK I. , ĈERNÝ J. , RAŜKOVÁ H. , VANÊĈEK J. , KUBIĈEK A. 
Published: April 2008

Ĉeleda, L., Urbanová, Z., Pavlásek, I., Ĉerný, J., Raŝkova, H., Vanêĉek, J. & Kubiĉek, A. The effect of intermittent treatment with sulphadimidine on coccidiosis in preruminant calves.J. vet. Pharmacol. Therap.8, 174–180.Preruminant calves excreted coccidia oocysts in their faeces after 3 weeks of group housing. Two weeks of oral sulphadimidine (SDM) administration, 50mg/kg on the first day of treatment followed by daily administration of 37.5mg/kg, under the same housing conditions kept the faeces free of oocysts. Three weeks later, these calves excreted oocysts again. Repetition of the same treatment for 2 weeks controlled the infection again, but a second treatment for 5 days did not suffice. The repeated long treatment affected immunoglobulin levels adversely. SDM given repeatedly at a lower dose rate (30mg/kg) for 1‐week periods with medication‐free intervals of 1 week controlled the infection and no adverse effects were noted. In comparison with controls, weight gains were greater in treated calves.L. Ĉeleda, Institute of Pharmacology, Albertov 4, 128 00 Prague 2, Czechoslovakia.
Pharmacokinetics of amikacin in the horse following intravenous and intramuscular administration
Authors: ORSINI J. A. , SOMA L. R. , ROURKE J. E. , PARK M. 
Published: April 2008

Orsini, J.A., Soma, L.R., Rourke, J.E. & Park M. Pharmacokinetics of amikacin in the horse following intravenous and intræmuscular administration. J. vet. Pharmacol. Therap. 8, 194–201.The pharmacokinetics of amikacin sulfate (AK) were studied in the horse after intravenous (i.v.) and intramuscular (i.m.) administration. Serum (Cs), synovial (Csf) and peritoneal (Cpf) fluid concentrations of the drug were measured. Doses of 4.4, 6.6 and 11.0 mg/kg were given. The concentrations at 15 min following i.v. injection were 30.3 ± 0.3, 61.2 ± 6.9 and 122.8 ± 7.4 (μg/ml, respectively, for the 4.4, 6.6 and 11.0 mg/kg doses. Mean peak Cs values after the intramuscular injections occurred at 1.0 h post‐injection and were 13.3 ± 1.6, 23.0 ± 0.6 and 29.8 ± 3.2 μg/ml, respectively. The t1/2 of amikacin was 1.44, 1.57 and 1.14 h for the 4.4, 6.6 and 11.0 mg/kg doses, respectively. In this study, minimum inhibitory concentrations (MIC) of amikacin sulfate were determined for six pathogens. Based on the MIC and the pharmacokinetic parameters, it would appear that the usual therapeutic dose of amikacin would be between 4.4 and 6.6 mg/kg twice daily and, for the more serious life‐threatening infections, dosing three times a day. J. A. Orsini, University of Pennsylvania, School of Veterinary Medicine, New Bolton Center Campus, Kennett Square, PA 19348, U.S.A.
Disposition of sulfadimidine and its N4‐acetyl and hydroxy metabolites in horse plasma
Authors: NOUWS J. F. M. , VREE T. B. , BAAKMAN M. , DRIESSENS F. , SMULDERS A. , HOLTKAMP J. 
Published: April 2008

Nouws, J.F.M., Vree, T.B., Baakman, M., Driessens, F., Smulders, A. & Holtkamp, J. Disposition of sulfadimidine and its N4‐acetyl and hydroxy metabolites in horse plasma. J. vet. Pharmacol. Therap. 8, 303–311.The plasma disposition of sulfadimidine (SDM) and its metabolites N4‐acetylsulfadimidine (N4‐SDM), 6‐hydroxymethyl‐4‐methyl‐pyrimidine (SCH2OH) and 5‐hydroxy‐4,6‐dimethyl‐pyrimidine (SOH), was studied in three horses following intravenous administration of SDM at dose levels of 20 and 200 mg/kg in cross‐over trials. The percentages of N4‐SDM (0.58‐0.90%), SOH (0.83‐6.75%) and SCH2OH (0.38‐0.71%) in plasma, expressed as a percentage of the total sulfonamide concentration, were small and their plasma concentrations were parallel with SDM from 4 h following administration. At high doses (200 mg/kg), the elimination half‐life was slightly longer than at low doses (6.0, 10.5, 11.0 vs 5.0, 9.5, 9.5, respectively). The plasma protein binding was related to the dose; it was for the 20 and 200 mg/kg doses, respectively:SDM:61.5–73.3% and 50.5–52.1%; SOH: 47.1–71.0% and 36.7–39.5%, and for N4‐SDM: 45.9–63.2% and 38.3–53.7%. The protein binding for SCH2OH, measured in samples obtained at the high dose level, ranged from 13.8 to 20.0%. Dr J. F. M. Nouws, RVV‐District 6, Wolfskuilseioeg 279, Nijmegen, Tlie Netherlands.
Radioimmunoassay of the anabolic agent zeranol. V. Residues of zeranol in the edible tissues, urine, faeces and bile of steers treated with Ralgro
Authors: DIXON S. N. , RUSSELL K. L. , HEITZMAN R.J. , MALLINSON C. B. 
Published: April 2008

Dixon, S.N., Russell, K.L., Hekzman, RJ. & Mallinson, C.B. Radioimmunoassay of the anabolic agent zeranol. V. Residues of zeranol in the edible tissues, urine, faeces and bile of steers treated with Ralgro. J. vet. Pharmacol. Therap. 9, 353–358.Two trials were conducted on steers implanted with zeranol (Ralgro) to determine the edible tissue residues and the secretion pattern in faeces, urine and bile of zeranol residues throughout and beyond the recommended withdrawal period (70 days) for this drug. In the first trial there was considerable variation in the zeranol residue concentration in all edible tissues, the highest concentrations found in the liver being significantly above the control values (P < 0.05). In the other tissues, only fat sampled 14 days after implanting was significantly above the control value (P < 0.05). The zeranol concentration in bile samples obtained at slaughter [70 days (18), 90 days (5) and 120 days (2)] were all higher than the apparent concentration in the bile of untreated steers. The mean concentration of zeranol in the faeces and urine varied from day to day and between animals sampled on the same day following implantation. The highest mean concentrations were observed during the first 40 days following implanting, declining steadily to approach the control values 70 days after implantation. The second trial using steers prepared with bile duct re‐entrant cannulae resulted in a similar pattern of zeranol excretion in bile, faeces and urine. The highest concentrations of zeranol were observed in bile and ranged from 24 to 34 μg/l; there was considerable variation between animals and within animals sampled on successive days. Although the concentration declined steadily, zeranol was still readily detectable 120 days after implanting. The residue data obtained in this study would suggest that although the most suitable biological samples for a monitoring programme would probably be bile and liver, it would be difficult to use residue data in these tissues to regulate the withdrawal period of zeranol.
Procainamide in the dog: antiarrhythmic plasma concentrations after intravenous administration
Authors: PAPICH MARK G. , DAVIS LLOYD E. , DAVIS CAROL A. 
Published: April 2008

Papich, M.G., Davis, L.E. & Davis, C.A. Procainamide in the dog: antiarrhythmic plasma concentrations after intravenous administration.J, vet. Pharmacol. Therap.9, 359–369.Procainamide hydrochloride was administered to ouabain‐intoxicated dogs to determine an antiarrhythmic plasma concentration of procainamide. Ventricular arrhythmias were produced in dogs following intravenous injections of ouabain. After a sustained ventricular tachycardia was achieved, procainamide was administered and plasma samples collected for assay. Plasma procainamide was assayed by fluorescence polarization immunoassay. Procainamide was administered at increasingly higher constant rate infusions in order to achieve intermittent, steady‐state plasma concentrations. Infusion rates were calculated on the basis of previous pharmacokinetic information.All six dogs that received procainamide converted to a normal sinus cardiac rhythm after attaining a mean plasma concentration of 33.8 μg/ml with a range of 48.5 μg/ml—25.0 μg/ml. It was observed that the computer‐generated prediction of plasma concentrations based upon previous pharmacokinetic data produced an underestimate of the actual plasma concentrations. These data may suggest that plasma concentrations of procainamide for controlling some cardiac arrhythmias in dogs may be higher than plasma concentrations cited for human patients.