摘要:

The acute effects of three doses ofcaptopril(12.5, 25, and 50 mg [approximately 0.5, 1.O, arid 2.0 mg/kg]) on several haemodynamic variables and plasma aldosterone concentration were investigated in four dogs with experimentally produced heart failure (rapid ventricular pacing) and one dog with dilated cardiomyopattiy. Haemodynamic variables were measured with a Swan‐Ganz ttierniodilution catheter and an indwelling carotid artery catheter at baseline and 1, 2, and 4 h after drug administration. A statistically significant (P<0.0.5) decrease in peripheral vascular resistance was observed 1 and 2 h following the 12.5 nig dose. A significant and large enough decrease in peripheral vascular resistance to produce a significant decrease in mean systemic arterial blood pressure was observed 1 and 2 ti after administering 25 and 50 mg of captopril.A mild but significant increase in cardiac output was observed 1 h after each dose. The drug effect on systemic arterial blood pressure lasted less than 4 h. No statistically significant changes were observed for the group in pulmonary capillary wedge pressure, right atrial blood pressure, or plasma aldosterone concentration at any time. We conclude that the acute haemodynamic benefits provided by captopril atlministration were mild and due primarily to arteriolar dilation. Doses of approximately 1–2 mg/kg produced slightly greater arteriolar dilation than an approximate dose of 0.5 mg/kg. The drug effect was short‐lived, lasting less tha

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00282.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Plasma lidocaine decay after injection was studied in five anaesthetized pigs and fitted to a two compartment open model. Derived pharniacokinetic paranieter‐s were eniployed to rapidly achieve plateau concentrations within 60 min of starting a two stage infusion of lidocaine hydrochloride. Hepatic extraction and clearance of lidocaine at steady state were determined in 10 pigs by transhep;ttic: sampling and nieasurenient of hepatic arterial and portal venous blood flow using perivascular ultrasonic flow probes placed at laparotomy. These data were compared with siniilar studies performed in man as well as the sheep, (log, monkey and cat. The lidocaine extraction ratio of 0.60 in the pig was found t o be similar to that determined by others in ma

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00283.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

This study was designed to determine if doses of aminophylline up to 10 mg/kg given i.v. would produce ventricular arrhythmias in seven healthy dogs anaesthetized with fentanyl‐dropelidol‐pentobarbital. Arrhythmias were sought by inspection of ECGs before and after attempts at provoking them with 5 pg/ kg boluses of epinephrine given i.v., or by programmed electrical stimulation. After cumulative doses of 10 nig aminophylline/kg body weight, producing an estimated plasma concentration of greater than 30 pginil, no ventricular ectopia other than escape depolarizations were observed. We were unable t o documentan arrhythmogenic effect of aminophylline when given rapidly by the i.v. route. I t is possible that the anaesthetic regimen reduced the arrhythmogenic property of aminophylline, or that arrhythmias might be produced in either obese or ill dogs; but it is unlikely that chronic administration of aminophylline would be more arrhythmoge

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00284.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The pharmacokinetics of pentoxifylline (P) and its alcohol metabolite I (MI) were determined after administration of intravenous pentoxifylline, sustained release pentoxifylline tablets (Trental®), and crushed pentoxifylline tablets in corn syrup, to five healthy adult horses. Pharmacokinetics were evaluated in a model‐independent manner. After intravenous administration, pentoxifylline was rapidly eliminated (mean residence time 1.09 f 0.67 h), had a large steady‐state volume of distribution (2.81 f 1.16 Vkg), and high clearance (3.06 51.05 I/kg/h). Oral absorption of pentoxifylline from both dose forms variedconsiderably between individuals. Times to peak concentration ranged from 1–10 h for either dose form. There was no difference in relative bioavailability (Fâ'™)between whole (0.98 k 0.30) and crushed Trental® tablets. Ratios between areas under the curve (AUC) for pentoxifylline and MI were different following administration of oral versus intravenous doses. This finding suggests that route of administration may affect the metabolic profile of pentoxifylline. Given the extreme differences in absorption characteristics between indi‐viduals in this study, recommendations are not made as to appropriate dose, dose interval, or dose form for administration of pentoxifylli

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00285.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Nicarbazin is an anticoccidial drug used mainly in birds, but also in rabbits. Besides the anticoccidial activity, riicarbazin has shown several other effects such as inhibition of growth and feed efficiency in poultries, and stimulation o f sugar intestinal absorption in rabbits. The present work has been performed in order to check whether nicarbazin also affects L‐leucine intestinal absorption. The results obtained show that nicarbazin decreases L‐leucine accumulation in the jejunal tissue, and increases mucosal to serosal transepithelial fluxes o f this amino acid in a dose‐dependent way, without modifying its diffusion across the intestinal epithelium. The drug stimulates the amino acid uptake in brush‐border and basolateral membrane vesicles, thus suggesting that nicarlxizin increases the absorption of L‐leucine mediated by

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00286.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The gastrointestinal (GI) distribution and plasma disposition kinetics of alberidazole (ABZ) metabolites after oral administration of netobirnin (NTB) to cattle were studied. Eight Holstein steers (150–180 kg) were surgically fitted with permanent cannulae in the rumen, abomasum and ileum. After post‐surgical recovery, the ariinials were treated orally with a suspension of neto1)imin zwitterion (400 mg/ml) at 20 nig/kg. Jugular blood and ruminal, abomasal arid ileal fluid samples were taken serially over a 96 h period and analysed by HPLC for NTB and its metabolites, including ABZ, ABZ sulphoxide (ABZSO), AH%sulphone (ABZSO?) and amino‐albendazole sulphone (NHp4BZSOy). N T B parent drug was only fonnd in the G I tract and for only 12–18 h post‐treatment. ABZSO and ABZSOp were the main metabolites found in plasma, being present for 30–36 h. These metabolites were exchanged between plasma and different GI fluids and were greatly concentrated in the abomasum. This phenornenori may account for the presence of ABZ, ABZSO and ABZSO? in the GI tract f'or 72 h post‐treatment despite the fact that ABZ was riot detected in plasma and ABZSO and ABZSO.;, were detected for only 30–36 h in plasma. The presence o f ABZ and ABZSO in the abomasum and intestine for this extended period of time is probably relevant for anthelmintic efficacy against GI parasites. The NH2ABZSO2metabolite was detected in plasma, abomasum and ileum and its disposition kinetics were characterized for

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00287.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

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 discus

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00288.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Sulphadimidine (20 mg/kg i.v.) plasma elimination and metabolite formation were studied in intact male, castrated male, and female dwarf goats. Plasma pharmacokinetics and urinary metabolite patterns were first studied in un‐treated animals. Afterwards, females and castrates were treated with a combination of testosterone‐propionate (1 mg/kg) and 17P‐oestradiolbenzoate(0.02 mg/kg) once every 3 days, for a period of 4 weeks. In untreated animals, males showed a considerably lower plasma clearance than females or castrates. This was accompanied by lower partial clearances for the production of two hydroxylated sulphadimidine metabolites. After hormonal treatment of females and castrates, sulphadimidine plasma clearance was significantly reduced, to values corresponding with those observed in control males. Furthermore, hydroxylation was significantly inhibited after treatment. The results indicate that sulphadimidine hydroxylation in the goat is performed by enzymes of the cytochrome P450 complex which are strongly influenced by gonadal hormones. Androgens seem to play a central role in this re

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00289.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

A regime for administration of ampicillin sodium by continuous intravenous infusions to horses was designed. The aim was to achieve plasma ampicillin concentrations between 5 and 10 pgiml over a 4‐h period. A 2 mgikg bodyweight loading dose of ampicillin sodium was administered intravenously at the beginning of the infusion in order to achieve steady‐state plasma concentra‐tions rapidly. The infusion system subsequently administered ampicillin at a rate of approximately 19.2 pglminikg bodyweight. The plasma concentrations obtained over the infusion period correlated very well with predicted calculations based on pharmacokinetic parameters. A mean ± SEM steady‐state plasma concentration (Cpss) of 5.94 ± 0.33 was obtained and ampicillin was shown to have an apparent steady‐state volume of distribution (Vdss) of 175.43 ± 13.63 ml/kg. When the pump was disconnected the concentrations declined over the following 4 h in an exponential way with an elimination half‐life (t1/2β) of 0.62 h. In addition, three different infusion dose rates (13.78, 19.34 and 2 l 4 8 pg/min/kg) were administered to a single animal showing that a good correlation(correlation coefficient>0.99) existed between the dose administered the steady‐state plasma concentrations and the corresponding areas under the plasma concentration

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00290.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Plasnia ronidazole concentrations were examined after intravenous (i.v.) antloral administration of ronidazole in sheep (t i = 6) at;I dosage of 5 mg/kg Iiody weight. In three sheep a ruminal and an abomasal fistula were inserted. l'heronidazole determinations were performed by an HPLC method. Oral bioav;iil‐ability in the fistulated sheep was only 5.5 k 1.8% (mean k SE). Somewhat lower values (4.6 k 1.45%) were obtained when the drug was administered through the ruminal fistula in the rumen. After administration of the sanie dose directly in the abomasum through the intraaboiiiasal fistula, 1)ioavailability was increased t o 86.0 k 8.9%. In the non‐fistulated sheep, oral biodisponibility was 2.6 k 0.5%.After water was restricted for 48 h before the oral ronidazole administration t othese sheep, bioavailability was slightly increased (6.0 k 9.1 %). When desmo‐pressin acetate was injected i.v. before the oral ronidazole;idministration,bioavailability was 10.6 k 6.5%. When glypressiii,;t1101her vasopressin analogue,was used, oral bioavailability was not influenced: 2.4 f 1.3%. Konitlazole wasalso incubated with ruminal contents antl the ronitlamle concer1tr;ition tle‐creased with a first order rate constant of ‘0.122 rfr 0.050 miri‐’ (mean f SF,).These results suggest that oral atfrniiiistration of ronidazole to sheep is o f littletherapeutic use, because most is metabolised by the ruminal triicro‐organisiiisbefore it can reach the circulation. A second conclusion we can make is that i t isvery difficult, if not impossible, at least with the methods used, to influencegastro‐intestinal motility in sheep to get a reprotlucahle closure of I heo

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00291.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY