Pharmacokinetics of famciclovir and penciclovir in tears following oral administration of famciclovir to cats: a pilot study     

Thomasy SM  Covert JC  Stanley SD  Maggs DJ 《Veterinary ophthalmology》2012,15(5):299-306

Objective To validate a means of collecting tears from cats, develop an assay for quantifying famciclovir and penciclovir in tears, and to assess famciclovir and penciclovir concentrations and pharmacokinetics in the tears of cats being treated orally with famciclovir for suspected herpetic disease. Animals Seven client‐owned cats. Procedures Cats were treated orally with a median (range) dose of 40 (39–72) mg of famciclovir/kg three times daily for at least 24 h. At various time points following famciclovir administration, tear samples were collected using Schirmer tear test strips. Tear famciclovir and penciclovir concentrations were measured using liquid chromatography‐mass spectrometry, and concentration‐time profiles were analyzed noncompartmentally. The relationship between famciclovir dose and tear penciclovir concentration near its maximum was evaluated using least squares linear regression. Results Maximum tear famciclovir concentration of 0.305 μg/mL occurred at 2.64 h; elimination half‐life was 2.28 h. Maximum tear penciclovir concentration (0.981 μg/mL) occurred 2.25 h following oral administration of famciclovir; elimination half‐life was 2.77 h. A significant positive correlation was noted between famciclovir dose and tear penciclovir concentration at various time points between 0.5 and 3.75 h following drug administration (P = 0.025). Tear penciclovir concentration exceeded the concentration shown to have in vitro efficacy against feline herpesvirus (FHV‐1) (0.304 μg/mL) in about half of samples collected. Conclusions Oral administration of 40 mg of famciclovir/kg to cats resulted in a tear penciclovir concentration‐time profile that approximated the plasma penciclovir concentration‐time profile and frequently achieved a penciclovir concentration at the ocular surface likely to be effective against FHV‐1.  相似文献   

Pharmacokinetics and pharmacodynamics of intravenous medetomidine in the horse     

Grimsrud KN  Mama KR  Steffey EP  Stanley SD 《Veterinary anaesthesia and analgesia》2012,39(1):38-48

ObjectiveTo describe the pharmacodynamics and pharmacokinetics following an intravenous (IV) bolus dose of medetomidine in the horse.Study designProspective experimental trial.AnimalsEight, mature healthy horses age 11.7 ± 4.6 (mean ± SD) years, weighing 557 ± 54 kg.MethodsMedetomidine (10 μg kg^?1) was administered IV. Blood was sampled at fixed time points from before drug administration to 48 hours post administration. Behavioral, physiological and biochemical data were obtained at predetermined time points from 0 minutes to 24 hours post administration. An algometer was also used to measure threshold responses to noxious stimuli. Medetomidine concentrations were determined by liquid chromatography-Mass Spectrometry and used for calculation of pharmacokinetic parameters using noncompartmental and compartmental analysis.ResultsPharmacokinetic analysis estimated that medetomidine peaked (8.86 ± 3.87 ng mL^?1) at 6.4 ± 2.7 minutes following administration and was last detected at 165 ± 77 minutes post administration. Medetomidine had a clearance of 39.6 ± 14.6 mL kg^?1 minute^?1 and a volume of distribution of 1854 ± 565 mL kg^?1. The elimination half-life was 29.1 ± 12.5 minutes. Glucose concentration reached a maximum of 176 ± 46 mg dL^?1 approximately 1 hour post administration. Decreased heart rate, respiratory rate, borborygmi, packed cell volume, and total protein concentration were observed following administration. Horses lowered their heads from 107 ± 12 to 20 ± 10 cm within 10 minutes of drug administration and gradually returned to normal. Horse mobility decreased after drug administration. An increased mechanical threshold was present from 10 to 45 minutes and horses were less responsive to sound.Conclusion and clinical relevance Behavioral and physiological effects following intravenous administration positively correlate with pharmacokinetic profiles from plasma medetomidine concentrations. Glucose concentration gradually transiently increased following medetomidine administration. The analgesic effect of the drug appeared to have a very short duration.  相似文献   

Surgical management and outcome of lower eyelid entropion in 124 cats     

White JS  Grundon RA  Hardman C  O'Reilly A  Stanley RG 《Veterinary ophthalmology》2012,15(4):231-235

Objectives To evaluate the success rate of various surgical techniques for the management of lower eyelid entropion in cats. Design Retrospective study. Animals studied One hundred and twenty‐four cats with surgical correction of lower eyelid entropion of 200 eyes over a 13 year period. Methods Records of 124 cats were reviewed for signalment, type of entropion, surgical procedure performed and post‐operative result. Results Combinations of the Hotz‐Celsus (HC), lateral canthal closure and full thickness wedge resection techniques were used to treat 64 bilateral and 60 unilateral cases of lower lid entropion. Twenty‐three cats were under a year of age, 52 cats were aged between 2 and 8 years and 49 were over 8 years old. The overall success rate for a single surgical procedure (which may consist of multiple techniques) to correct lower eyelid entropion was 96.0% per eye. The remaining 4.0% had the entropion resolved with a second surgery. A combined HC and lateral canthal closure had a 99.21% success rate of resolving lower lid entropion. Geriatric cats were the most likely age group to develop corneal sequestra; 37% of cats in this group presented with entropion and corneal sequestra concurrently. Seventeen percent of cats that presented with unilateral entropion and did not have prophylactic surgery on the fellow eye went on to develop entropion in the fellow eye. Conclusions A combined HC and lateral canthal closure was the most effective surgical technique in managing lower eyelid entropion of cats in our study. Prophylactic lateral canthal closure in the unaffected eye is recommended.  相似文献   

Plasma concentrations,behavioural and physiological effects following intravenous and intramuscular detomidine in horses     

K. R. Mama  K. Grimsrud  T. Snell  S. Stanley 《Equine veterinary journal》2009,41(8):772-777

Reasons for performing study: Detomidine hydrochloride is used to provide sedation, muscle relaxation and analgesia in horses, but a lack of information pertaining to plasma concentration has limited the ability to correlate drug concentration with effect. Objectives: To build on previous information and assess detomidine for i.v. and i.m. use in horses by simultaneously assessing plasma drug concentrations, physiological parameters and behavioural characteristics. Hypothesis: Systemic effects would be seen following i.m. and i.v. detomidine administration and these effects would be positively correlated with plasma drug concentrations. Methods: Behavioural (e.g. head position) and physiological (e.g. heart rate) responses were recorded at fixed time points from 4 min to 24 h after i.m. or i.v. detomidine (30 μg/kg bwt) administration to 8 horses. Route of administration was assigned using a balanced crossover design. Blood was sampled at predetermined time points from 0.5 min to 48 h post administration for subsequent detomidine concentration measurements using liquid chromatography‐mass spectrometry. Data were summarised as mean ± s.d. for subsequent analysis of variance for repeated measures. Results: Plasma detomidine concentration peaked earlier (1.5 min vs. 1.5 h) and was significantly higher (105.4 ± 71.6 ng/ml vs. 6.9 ± 1.4 ng/ml) after i.v. vs. i.m. administration. Physiological and behavioural changes were of a greater magnitude and observed at earlier time points for i.v. vs. i.m. groups. For example, head position decreased from an average of 116 cm in both groups to a low value 35 ± 23 cm from the ground 10 min following i.v. detomidine and to 64 ± 24 cm 60 min after i.m. detomidine. Changes in heart rate followed a similar pattern; low value of 17 beats/min 10 min after i.v. administration and 29 beats/min 30 min after i.m. administration. Conclusions: Plasma drug concentration and measured effects were correlated positively and varied with route of administration following a single dose of detomidine. Potential relevance: Results support a significant influence of route of administration on desirable and undesirable drug effects that influence case management.  相似文献   

Pharmacokinetics of penciclovir in healthy cats following oral administration of famciclovir or intravenous infusion of penciclovir     

Thomasy SM  Whittem T  Bales JL  Ferrone M  Stanley SD  Maggs DJ 《American journal of veterinary research》2012,73(7):1092-1099

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On the Interpretation of the Markings on Mars     

Stanley HM 《Science (New York, N.Y.)》1892,20(507):235-236

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Epidemiologic evaluation of diarrhea in dogs in an animal shelter     

Sokolow SH  Rand C  Marks SL  Drazenovich NL  Kather EJ  Foley JE 《American journal of veterinary research》2005,66(6):1018-1024

OBJECTIVES: To determine associations among infectious pathogens and diarrheal disease in dogs in an animal shelter and demonstrate the use of geographic information systems (GISs) for tracking spatial distributions of diarrheal disease within shelters. SAMPLE POPULATION: Feces from 120 dogs. PROCEDURE: Fresh fecal specimens were screened for bacteria and bacterial toxins via bacteriologic culture and ELISA, parvovirus via ELISA, canine coronavirus via nested polymerase chain reaction assay, protozoal cysts and oocysts via a direct fluorescent antibody technique, and parasite ova and larvae via microscopic examination of direct wet mounts and zinc sulfate centrifugation flotation. RESULTS: Salmonella enterica and Brachyspira spp were not common, whereas other pathogens such as canine coronavirus and Helicobacter spp were common among the dogs that were surveyed. Only intestinal parasites and Campylobacterjejuni infection were significant risk factors for diarrhea by univariate odds ratio analysis. Giardia lamblia was significantly underestimated by fecal flotation, compared with a direct fluorescent antibody technique. Spatial analysis of case specimens by use of GIS indicated that diarrhea was widespread throughout the entire shelter, and spatial statistical analysis revealed no evidence of spatial clustering of case specimens. CONCLUSIONS AND CLINICAL RELEVANCE: This study provided an epidemiologic overview of diarrhea and interacting diarrhea-associated pathogens in a densely housed, highly predisposed shelter population of dogs. Several of the approaches used in this study, such as use of a spatial representation of case specimens and considering multiple etiologies simultaneously, were novel and illustrate an integrated approach to epidemiologic investigations in shelter populations.  相似文献   

Clinical, histopathological and immunological characteristics of exfoliative cutaneous lupus erythematosus in 25 German short-haired pointers     

Bryden SL  White SD  Dunston SM  Burrows AK  Olivry T 《Veterinary dermatology》2005,16(4):239-252

Clinical, histopathological and immunological features of exfoliative cutaneous lupus erythematosus, an uncommon generalized exfoliative dermatitis occurring exclusively in German short-haired pointers, were characterized in 25 dogs. The disease affects young adult dogs and its familial incidence strongly suggests a hereditary origin. Lesions were characterized by scaling and alopecia affecting 100 (25/25) and 76% (19/25) of dogs, respectively. Follicular casts were present in 28% (7/25) of dogs. The muzzle, pinnae and dorsum were typically affected. Generalized skin lesions were described in 52% (13/25) of dogs. Systemic signs of pain and lameness affected several dogs. Anaemia and thrombocytopenia were detected in several dogs with a more severe clinical phenotype. The most common histopathological features were hyperkeratosis and a lymphocytic interface dermatitis. Direct immunostaining revealed IgG deposition in the epidermal and follicular basement membrane of 100 (19/19) and 41% (7/17) of dogs, respectively. Circulating antifollicular and antisebaceous gland IgG antibodies were demonstrated by indirect immunostaining in 57% (4/7) of dogs. This disease usually responds poorly to immunosuppressive therapy and it has a guarded prognosis. Where outcome was recorded, 85% (10/12) of dogs were euthanased due to either a failure to respond to, or complications associated with, immunomodulatory therapy. Two affected dogs are in remission and maintained on immunomodulatory dosages of prednisolone. This study demonstrates the existence of a cellular and humoral immune response directed against the epidermal basement membrane of dogs with exfoliative cutaneous lupus erythematosus. Additional studies are required to further characterize the immunological pathogenesis of this disease.  相似文献   

Zanthoxylum piperitum (DC), a potential feeding deterrent for mammals: studies with Microtus ochrogaster (Wagner)     

Epple G  Bryant BP  Mezine I  Lewis S 《Pest management science》2004,60(7):624-630

Total extract from the fruit of Szechuan pepper (Zanthoxylum piperitum DC), the volatile components of the extract and a non‐volatile fraction containing alkylamides (NVA fraction) are feeding deterrents for rats. The present study investigated the effectiveness of these natural repellents in prairie voles (Microtus ochrogaster Wagner). Two‐choice feeding trials were conducted during which food‐deprived voles were offered choices between oat‐bran wafers. In Experiment 1, 10 voles were given three sets of feeding trials, each 2 h long. Baseline consumption was established during the first set of two trials by offering a choice between two oat‐bran wafers dipped in ethanol, the control solvent. During the second set of two trials the voles were given a choice between an oat‐bran wafer dipped in ethanol and a wafer dipped in Zanthoxylum extract. During the third set the voles were given a choice between a wafer served on top of a screened dish containing a sample of ethanol and a wafer served on top of a dish containing a sample of extract. In this manner the voles were exposed to volatile compounds emanating from the extract but could not contact it. Wafers dipped in extract were almost completely avoided. The volatile components of extract also significantly reduced food intake. In Experiment 2, habituation to the volatile constituents of extract was examined in 16 Zanthoxylum‐naïve voles. Baseline consumption was established by offering two wafers served on top of screened dishes containing ethanol. This was followed by twelve tests during which a choice between a wafer served above a sample of ethanol and a wafer served above a sample of extract was given. The voles failed to habituate to the volatile components of extract, consistently consuming less of the wafers served above extract. In Experiment 3 a dose‐response curve to Zanthoxylum extract was established, using 12 stimulus‐naïve voles. After baseline consumption was established, the animals were given two tests each, presenting a choice between a control wafer and a wafer dipped in a dilution of extract (0.001–100 g liter^?1). Only concentrations of 10 and 100 g liter^?1 reduced food intake. In Experiment 4 the effects of the non‐volatile fraction of extract were compared to those of whole extract. Vegetable oil was used as solvent. Eight stimulus‐naïve voles were given two tests with a choice between an oil‐dipped and an extract‐dipped wafer. A second group of eight voles received two tests with a choice between an oil‐dipped and NVA‐dipped wafer. Extract‐dipped wafers were avoided, but the NVA fraction had no effect on food consumption. Copyright © 2004 Society of Chemical Industry  相似文献   

Comparison of direct immunofluorescence, modified acid-fast staining, and enzyme immunoassay techniques for detection of Cryptosporidium spp in naturally exposed kittens     

Marks SL  Hanson TE  Melli AC 《Journal of the American Veterinary Medical Association》2004,225(10):1549-1553

OBJECTIVE: To evaluate a modified Ziehl-Neelsen acid-fast staining technique (mZN), a direct immunofluorescence detection procedure (DIF), and 3 commercial enzyme immunoassays (EIAs) for detection of Cryptosporidium oocysts in fecal specimens from kittens. DESIGN: Prospective study. SAMPLE POPULATION: 416 fecal specimens collected from 104 randomly selected domestic shorthair kittens (8 to 16 weeks of age) that were naturally exposed to Cryptosporidium spp. PROCEDURE: Fresh fecal specimens were collected once daily for 4 consecutive days and processed immediately. Sensitivities of mZN, DIF, and 3 commercial EIAs (EIA-1, EIA-2, and EIA-3) were estimated and compared. RESULTS: EIA-2 had the highest sensitivity on day 1 (89%), followed by EIA-1 (80%), and mZN (72%). EIA-3 had the lowest sensitivity on day 1 (15%). EIA-2, EIA-1, and mZN had similar sensitivities after 2 consecutive fecal examinations (approx 90%). Determination of specificities was compromised by the small number of cats that had negative results for all tests (n = 3). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that EIA-2 and EIA-1 had the highest sensitivities when only a single fecal specimen was examined; however, mZN and EIA-1 had similar sensitivities when 2 consecutive fecal specimens were examined. The higher costs of EIA-2 and EIA-1 may be offset by the tests' high sensitivity, simplicity of use, and ease of interpretation and by savings in technician time.  相似文献