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Biomedical subjects

A I Webb

Publications and source records attributed to A I Webb.

At least 19 recordsLinked to original sources
PubMed1999

The Food Animal Residue Avoidance Databank (FARAD). Past, present and future.

During the last one-and-one-half decades, FARAD has established an unparalleled compilation of residue and pharmacokinetic information for veterinary species. In order to fulfill its mission, FARAD has become as much a research project as an educational one. Pressing problems, such as disease-altered kinetics, minor-species drug use, and industrial contaminants in livestock, require the new methods of analysis FARAD is developing. The data upon which this work is based can be greatly augmented by participation by other nations. In the United States, it was the cooperation of both academic and regulatory organizations that made the success of FARAD possible. Similar international cooperation can facilitate use of the FARAD model in other countries for the economic benefit of all participants, enhancement of food safety, and promotion of animal welfare.

Animals↗
PubMed1999

Effect of respiratory tract disease on pharmacokinetics of tilmicosin in rats.

BACKGROUND AND PURPOSE: In rats, murine respiratory mycoplasmosis is caused by Mycoplasma pulmonis. Tilmicosin, a macrolide antibiotic, has good tissue penetration and reaches high concentration in the lungs. Therefore, a model for studying the effects of disease on pharmacokinetics of tilmicosin was developed, using LEW rats. METHODS: Seventy-two LEW rats were assigned at random to two groups: one group was inoculated with M. pulmonis, and the other served as an uninoculated control group. On postinoculation day 31, all rats received a single dose of tilmicosin (20 mg/kg of body weight, subcutaneously). RESULTS: Concentration of tilmicosin in the lungs of both groups of rats was significantly higher than serum tilmicosin concentration at all times. Infected rats had significantly higher lung tilmicosin concentration than did noninfected rats. No correlation was found between pH of the lungs and tilmicosin concentration in the lungs in either treatment group, nor did treatment have any effect on pH of the muscle. CONCLUSION: Tilmicosin accumulates in the lungs, and infection/inflammation further improves its tissue penetration.

Animals↗
PubMed1998

Pharmacokinetics and pharmacodynamics of tilmicosin in sheep and cattle.

Tilmicosin is a long-acting macrolide antibiotic currently approved for treatment of bovine respiratory disease in the USA. Serum pharmacokinetics of tilmicosin were compared between cattle (major species) and sheep (minor species) after subcutaneous injection in order to evaluate a new potential application of the drug in currently nonapproved species. There were no significant differences in the elimination rates, maximum serum concentrations, half-lives (t1/2), areas under the curve (AUC), areas under the first-moment curve (AUMC), and mean residence times. Volume of distribution (Vd(area)) and clearance (Cl), when normalized by body weight, were also similar. The only significantly different parameter was time at which maximum drug concentration was reached (tmax), with sheep having the tmax of 3.9 h, compared to 0.5 h in cattle. Although macrolides are considered to be one of the safest anti-infective drugs, adverse cardiovascular effects of several macrolides have been reported. The cardiopulmonary effects of tilmicosin were monitored in healthy adult sheep after receiving a single subcutaneous (s.c.) injection of tilmicosin at the dose of 10 mg/kg, and no significant changes were found. The study indicates that tilmicosin can be used safely and effectively in sheep at the given dose, with no adverse cardiopulmonary effects.

Animals↗
PubMed1998

Development and use of an enzyme-linked immunosorbent assay to monitor serum and urine acepromazine concentrations in thoroghbreds, and possible changes associated with exercise.

OBJECTIVES: To develop an ELISA that is sensitive and suitable for measurement of immunoreactive acepromazine (ACP) in horse serum and urine and to determine the acute effects of exercise on immunoreactive ACP values in Thoroughbreds. ANIMALS: 12 healthy Thoroughbreds (5 mares, 5 geldings, 2 stallions), aged 2 to 8 years. PROCEDURE: A commercially available antibody and a horseradish peroxidase-conjugated oxime derivative of immunoreactive ACP were used to develop a one-step ELISA. Horses were used in a crossover design study to evaluate possible effects of treadmill exercise on serum and urine ACP concentrations after a single (25 mg) IM injection of the drug. RESULTS: Immunoreactive ACP was detectable at concentrations as low as 50 pg/ml in serum and 100 pg/ml in urine, with intra- and interassay variabilities of 1.1 and 5.2%, respectively. The antibody had some cross-reactivity with a limited number of other phenothiazines. After drug administration, serum ACP immunoreactivity achieved a peak concentration (10.5 ng/ml) within 30 minutes and could be measured up to 48 hours in serum and 120 hours in urine. Although exercise had no significant effect on serum drug concentration, immunoreactive ACP disappeared more quickly (by 48 hours) from the urine of horses in the exercised group. CONCLUSIONS: This one-step ELISA provides a simple and sensitive means to measure immunoreactive ACP in equine serum and urine. The ability to detect drug several days after administration of a low dose of ACP should augment efforts to control illicit use of this drug in performance horses. Potential changes in ACP kinetics after exercise warrant further study.

Acepromazine↗
PubMed1997

Intravenous and oral pharmacokinetic evaluation of a 2-hydroxypropyl-beta-cyclodextrin-based formulation of carbamazepine in the dog: comparison with commercially available tablets and suspensions.

Complexation of carbamazepine with 2-hydroxypropyl-beta-cyclodextrin was performed to provide improved formulations of this widely used antiepileptic drug. Based on this approach, liquid dosage forms were configured for both parenteral and oral use. Intravenous administration of an aqueous carbamazepine x 2-hydroxypropyl-beta-cyclodextrin (CBZ x HPbetaCD) complex at a CBZ dose of 20 mg/kg was well tolerated and generated high initial drug levels that fell monoexponentially as a function of time, yielding a plasma elimination half-life of 38 min. Oral studies were completed with three preparations: a commercially available tablet and suspension, as well as a CBZ x HPbetaCD oral solution. Oral administration of tablets gave erratic and slow absorption, leading to maximum CBZ concentrations (C(max)) of <2 microg/mL, which were manifested only at 2.5 h after drug dosing. The absolute bioavailability of CBZ from the tablets was approximately 25%. Both the suspension and CBZ x HPbetaCD solution gave a significantly improved profile. Thus, the liquid oral dosage forms approximately doubled the oral bioavailability of CBZ compared with the tablets.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1997

Evaluation of a brain-targeting zidovudine chemical delivery system in dogs.

AIDS encephalopathy is an insidious complication of human immunodeficiency virus infection which is difficult to treat because of the poor uptake of many potentially useful antiretroviral drugs through the blood-brain barrier. A chemical delivery system (CDS) for zidovudine (AZT) based on redox trapping within the brain has been prepared and tested in several animal models to circumvent this limitation. The behavior of the AZT-CDS in the dog was considered. Parenteral administration of AZT resulted in rapid systemic elimination and poor uptake by the central nervous system. Ratios of the area under the concentration-time curve of AZT for cerebrospinal fluid to that for blood were 0.32, and ratios of the area under the concentration-time curve of AZT for brain to that for blood were approximately 0.25. Administration of an aqueous formulation of the AZT-CDS resulted in rapid tissue uptake and conversion of the CDS to the corresponding quaternary salt with the subsequent production of AZT. Delivered in this way, the levels of AZT in brain were 1.75- to 3.3-fold higher than those associated with conventional AZT administration. In addition, the levels of AZT in blood were 46% lower than those associated with AZT administration. The higher concentrations in brain and lower concentration in blood combined to significantly increase the ratio of the concentration of AZT in the brain to that in blood after AZT-CDS administration compared to that after AZT dosing.

Animals↗
PubMed1996

Evidence for a relation between inspired gas mixture and the left ventricular contrast achieved with Albunex in a canine model.

BACKGROUND: In a previous experiment, a marked reduction in the right- and left-sided contrast effect of Albunex was noted in an intubated animal spontaneously breathing isoflurane in 100% oxygen. The theory suggests that the time course of echogenicity of microbubbles in liquid is dependent on the pressure and the gradients of dissolved gases. The present set of experiments tested whether the loss of contrast occurs at commonly used therapeutic concentrations of inspired oxygen. HYPOTHESIS: This research tested the hypothesis that the left ventricular (LV) contrast effect achieved with intravenous injection of the ultrasound contrast agent Albunex is related to the inspired oxygen content. METHODS: Intubated dogs were maintained in a spontaneously respiring anesthetic state on isoflurane and mixtures of oxygen (12-50%) in nitrogen. FIO2 was held steady for 15 min prior to injection of 0.08 ml/kg of Albunex. The contrast effects were recorded from a transthoracic short-axis view. Left and right ventricular brightness curves were generated from digitized sequences of end-diastolic frames. The minimum and maximum brightness and area under the time-brightness curves were determined. RESULTS: The LV maximum brightness and area under the curve showed significant negative correlations (p = < 0.004) with the FIO2, while the minimum brightness showed a significant positive correlation (p = < 0.002). No significant correlations were found for the right ventricular brightness parameters. CONCLUSIONS: These findings show an important relationship between the FIO2 and loss of the contrast effect of Albunex. This loss occurs at oxygen concentrations in the therapeutic range, but could be overcome by increasing the dose of Albunex. The mechanism is likely related to an outward nitrogen gradient causing a loss of echogenicity. The clinical implication is that patients on supplemental oxygen may require higher doses of Albunex to achieve optimal opacification.

Albumins↗
PubMed1994

Pharmacokinetics and pharmacodynamics of acepromazine in horses.

A specific, sensitive, reverse-phase high-performance liquid chromatographic assay for acepromazine, with analytic sensitivity as low as 5 ng/ml of plasma, and electrochemical detection with an oxidation potential of 0.7 V, was used to study the pharmacokinetics of acepromazine given at a dosage of 0.15 mg/kg of body weight in horses. The relation between effect and pharmacokinetics of the drug was examined. The effects studied included those on blood pressure, pulse, PCV, measures of respiration function, and sedation. Intravenously administered doses led to a biphasic concentration decay pattern with an alpha-phase distribution half-life of < 3 minutes. The beta-phase half-life was in the range of 50 to 150 minutes. The CNS effects peaked at 20 minutes after administration, and the hemodynamic effects peaked at 100 minutes. In all horses, the most sensitive variable was the PCV, which decreased by up to 20% (P < 0.0001). Systolic, diastolic, and mean blood pressures decreased (P < 0.0001); heart rate was unchanged (P > 0.05). Neither blood gas tensions nor blood pH changed noticeably (P > 0.05). In all horses studied, acepromazine had a significant (P < 0.0001) sedative effect, as observed by posture and alertness. None of the observed pharmacodynamic effects correlated well with plasma acepromazine concentration. These effects persisted beyond the time of detectable acepromazine concentration, indicating that they might be caused by active metabolites, or that their timing could result from complex pharmacokinetic compartment influences.

Acepromazine↗
PubMed1993

Propofol in rabbits. 1. Determination of an induction dose.

Propofol was evaluated as an intravenous agent for induction of anesthesia in 94 non-premedicated New Zealand White rabbits (mean body weight 3.25 kg). Lack of chewing oral introduction of an endotracheal tube was chosen as the end-point in signaling loss of consciousness. A rapid and excitement-free loss of consciousness was observed. Using probit analysis, a 50% effective dose of 6.44 mg/kg was calculated. No statistically significant difference between genders was shown. Independent of the dose administered, recovery was rapid and smooth.

Anesthesia↗
PubMed1993

Propofol in rabbits. 2. Long-term anesthesia.

The cardiopulmonary effects of propofol as the sole anesthetic agent administered as a continuous intravenous infusion over 8 hours were evaluated in ten ventilated New Zealand White rabbits. Heart rate, mean blood pressure, arterial oxygen and carbon dioxide tensions, arterial pH, hemoglobin's saturation with oxygen, packed cell volume, and temperature were continuously monitored and recorded at 0 (baseline), 30, 60, 120, 180, 240, 300, 360, 420, and 480 minutes and then hourly for up to 4 hours during recovery. Only light planes of anesthesia could be achieved with a mean propofol infusion rate of 0.876 mg/kg/min. Hypotension and hypoxemia were common features. Four rabbits did not survive the study period and recovery was slow in the surviving animals. With monitoring being the same, Intralipid 10%, the vehicle of propofol, infused into two rabbits (controls) had no adverse effects. Intravenous administration of propofol alone cannot be recommended for long-term anesthesia in the rabbit. Oxygen supplementation appears to be an important element in improving quality of anesthesia and outcome.

Anesthesia↗
PubMed1989

Pulmonary vascular reactivity of the newborn pony foal.

Adult ponies develop pulmonary hypertension at altitude (Bisgard, Orr and Will 1975), but the neonatal response to acute hypoxaemia is unknown. Seven foals aged five days were instrumented with a systemic and a Swan-Ganz pulmonary artery catheter while anesthetised and intubated. Cardiac index, pulmonary (PAP) and systemic (SAP) vascular pressures were measured as the foals breathed gas mixtures with FI02 of 8 to 94 per cent. Because foramen ovale or ductus arteriosus shunts might have altered thermodilution cardiac index measurements in the stressed foals, the ratio, PAP/SAP was calculated to define relative circulatory reactivity. Three foals, two of which were full siblings, had very marked elevation of PAP/SAP from 0.6 to 1.41 at low inspired oxygen tensions. Four different foals attained maximal PAP/SAP of only 0.2 to 0.92 at similarly low oxygen tensions (P less than 0.0001). Thus, pulmonary vascular reactivity to ventilatory hypoxaemia varied greatly in pony foals of the same age. The exaggerated reactivity in related foals suggested that, as in cattle, a genetic predisposition to develop reactive pulmonary hypertension under hypoxaemic stress may exist.

Animals↗
PubMed1989

Plasma and erythrocyte cholinesterase values for the common long-nosed armadillo, Dasypus novemcinctus.

Plasma and erythrocyte cholinesterase activities were determined for 40 free-living and 12 captive common long-nosed armadillos (Dasypus novemcinctus) in order to establish normal values for monitoring pesticide exposure. Plasma cholinesterase activity ranged from 105 to 549 U/liter with no sexual or seasonal differences. Plasma values from captive animals were significantly lower than those from wild armadillos. Erythrocyte cholinesterase activity ranged from 2,915 to 15,126 U/liter with no differences detected between captive and wild animals or between sexes. However, erythrocyte cholinesterase values varied seasonally. Erythrocyte and plasma cholinesterase activities were not significantly correlated. Packed cell volume ranged from 24 to 51% and did not vary significantly between captive and wild samples, between sexes or among seasons. However, both whole blood and erythrocyte cholinesterase activities showed significant negative correlations with packed cell volume. Controlled experiments are needed to find the factors responsible for the statistically significant difference between plasma cholinesterase activities of captive and wild armadillos. The seasonal variation in erythrocyte cholinesterase activity and the negative correlation between erythrocyte cholinesterase activity and packed cell volume can be explained by an hypothesis that relates the variation in erythrocyte cholinesterase activity to variation in erythrocyte turnover rate. Future work should involve experiments to test this hypothesis.

Animals↗
PubMed1988

Use of halothane to maintain anesthesia induced with etorphine in juvenile African elephants.

Sixteen 3- to 5-year-old African elephants were anesthetized one or more times for a total of 27 diagnostic and surgical procedures. Xylazine (0.1 +/- 0.04 mg/kg of body weight, mean +/- SD) and ketamine (0.6 +/- 0.13 mg/kg) administered IM induced good chemical restraint in standing juvenile elephants during a 45-minute transport period before administration of general anesthesia. After IM or IV administration of etorphine (1.9 +/- 0.56 micrograms/kg), the mean time to lateral recumbency was 20 +/- 6.6 and 3 +/- 0.0 minutes, respectively. The mean heart rate, systolic blood pressure, and respiration rate during all procedures was 50 +/- 12 beats/min, 106 +/- 19 mm of Hg, and 10 +/- 3 breaths/min, respectively. Cardiac arrhythmias were detected during 2 procedures. One elephant with hypotension responded to a decrease in the concentration of halothane and IV infusion of dobutamine HCl. Alterations in systolic blood pressure, ear flapping, and trunk muscle tone were useful for monitoring depth of anesthesia. Results indicated that halothane in oxygen was effective for maintenance of surgical anesthesia in juvenile African elephants after induction with etorphine.

Anesthesia↗