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Pharmacokinetics of norfloxacin in dogs after single intravenous and single and multiple oral administrations of the drug 总被引:3,自引:0,他引:3
S A Brown J Cooper J J Gauze D S Greco D W Weise J M Buck 《American journal of veterinary research》1990,51(7):1065-1070
Norfloxacin was given to 6 healthy dogs at a dosage of 5 mg/kg of body weight IV and orally in a complete crossover study, and orally at dosages of 5, 10, and 20 mg/kg to 6 healthy dogs in a 3-way crossover study. For 24 hours, serum concentration was monitored serially after each administration. Another 6 dogs were given 5 mg of norfloxacin/kg orally every 12 hours for 14 days, and serum concentration was determined serially for 12 hours after the first and last administration of the drug. Complete blood count and serum biochemical analysis were performed before and after 14 days of oral norfloxacin administration, and clinical signs of drug toxicosis were monitored twice daily during norfloxacin administration. Urine concentration of norfloxacin was determined periodically during serum acquisition periods. Norfloxacin concentration was determined, using high-performance liquid chromatography with a limit of detection of 25 ng of norfloxacin/ml of serum or urine. Serum norfloxacin pharmacokinetic values after single IV dosing in dogs were best modeled, using a 2-compartment open model, with distribution and elimination half-lives of 0.467 and 3.56 hours (harmonic means), respectively. Area-derived volume of distribution (Vd area) was 1.77 +/- 0.69 L/kg (arithmetic mean +/- SD), and serum clearance (Cls) was 0.332 +/- 0.115 L/h/kg. Mean residence time was 4.32 +/- 0.98 hour. Comparison of the area under the curve (AUC; derived, using model-independent calculations) after iv administration (5 mg/kg) with AUC after oral administration (5 mg/kg) in the same dogs indicated bioavailability of 35.0 +/- 46.1%, with a mean residence time after oral administration of 5.71 +/-2.24 hours. Urine concentration was 33.8 +/- 15.3 micrograms/ml at 4 hours after a single dose of 5 mg/kg given orally, whereas concentration after 20 mg/kg was given orally was 56.8 +/- 18.0 micrograms/ml at 6 hours after dosing. Twelve hours after drug administration, urine concentration was 47.4 +/- 20.6 micrograms/ml after the 5-mg/kg dose and 80.6 +/- 37.7 micrograms/ml after the 20/mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Haerdi-Landerer MC Suter MM Steiner A 《American journal of veterinary research》2007,68(12):1324-1331
Objective-To evaluate local tissue compatibility of doxycycline hyclate (DOX) in antebrachiocarpal joints of calves. Animals-10 healthy calves between 80 and 110 kg. Procedures-Calves were assigned to 2 treatment groups. Calves in groups DOX(low) and DOX(high) were administered 5 and 10 mg of DOX, respectively, locally in 1 antebrachiocarpal joint. The contralateral joint served as a control joint and was injected with 0.9% NaCl solution. General and local clinical findings were scored. Several variables were assessed in blood and synovial fluid for 9 days. Calves were euthanatized and pathologic changes and drug residues evaluated. Results-Throughout the study, none of the calves had clinical changes or abnormal hematologic values. Significant differences between treatment and control joints were evident only for matrix metalloproteinases at 0.5 hours after injection, with less activity for the DOX-treated joints in both treatment groups. Values for all synovial fluid variables, except nitric oxide, increased significantly during the first 12 to 72 hours after arthrocentesis in control and DOX-treated joints. Histologic examination revealed minimal infiltration of inflammatory cells independent of the treatment. No drug residues were detected 9 days after arthrocentesis in any tissues obtained from the liver, kidneys, fat, and skeletal muscles. Conclusions and Clinical Relevance-DOX had excellent intra-articular compatibility in healthy calves. Arthrocentesis induced a mild transient increase of inflammatory mediators in the synovial fluid. Significant decreases in matrix metalloproteinase activity in DOX-treated joints may indicate a potential chondroprotective effect of DOX. 相似文献
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OBJECTIVE: To determine the effect of intra-articular gentamicin-impregnated polymethylmethacrylate (PMMA) beads inserted in the equine tarsocrural joint on the synovial fluid, synovial lining, and cartilage, and to determine the peak and sustainable gentamicin concentrations in synovial fluid and plasma. STUDY DESIGN: Pharmacokinetic, cytologic, and histologic study of the effect of gentamicin-impregnated PMMA on normal equine tarsocrural joints. ANIMALS: Five healthy adult horses. METHODS: Gentamicin-impregnated PMMA bead strands (3 strands each of 40 beads, with each strand containing 100 mg gentamicin) were surgically inserted into one radiographically normal tarsocrural joint in 5 horses. Each horse had both joints flushed with 1 L of lactated Ringer's solution before bead administration. Synovial fluid total protein concentration, white blood cell (WBC) count, gentamicin concentration, synovial histology, cartilage integrity, and cartilage glycosaminoglycan (GAG) concentrations were determined. RESULTS: Gentamicin concentration (mean +/- SEM peak concentration, 27.9 +/- 2.27 microg/mL) occurred in the first 24 hours and remained above 2 microg/mL for 9 days. Gentamicin concentrations in control joints and the plasma remained below detectable levels. The synovial fluid WBC count for treated joints was increased compared with control joints for 72 hours, but was similar at day 6. The synovial protein concentration in gentamicin-treated joints remained increased for 21 days. Synovium in treated joints had diffuse synovitis, whereas control joints had less fibrovascular proliferation. Superficial cartilage erosion was present in all treated joints. There was no difference in the GAG content of treated and control joint cartilage. CONCLUSIONS: Short-term implantation of gentamicin (300 mg)-impregnated PMMA beads can provide therapeutic levels of gentamicin (>2 microg/mL) in the normal tarsocrural joint for 9 days; however, gentamicin-impregnated PMMA beads induce synovitis and superficial cartilage erosion. CLINICAL RELEVANCE: Temporary intra-articular administration of antibiotic-impregnated PMMA may be an effective way to treat septic joints that require constant high concentrations of antibiotics. 相似文献
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L. Mark Haugland DVM Michael A. Collier DVM Diplomate ACVS L.E. DeBault PhD Robert C. Walls PhD Luis Flavio Geo de Siqueira DVM 《Journal of Equine Veterinary Science》1995,15(6)
Eight mature horses were administered a single intramuscular injection of 500 mg polysulfated glycosaminoglycan (PSGAG) labeled with 2.044 mCi tritium. Synovial fluid samples were collected from the antebrachiocarpal (carpal), metacarpophalangeal (fetlock), tibiotarsal (hock) and coronopedal (coffin) joints prior to injection and at 2, 4, 8, 12, and 24 hours after injection. The samples were subjected to scintillation counting in decays per minute and were converted to μg PSGAG per ml. The levels achieved in the synovial fluid of the various joints were compared to levels of PSGAG described as adequate to inhibit enzymes which degrade articular cartilage matrix components and hyaluronic acid and adequate to stimulate production of new matrix components and hyaluronic acid in diseased joints.Mean synovial fluid 3H-PSGAG levels indicated that peak concentrations of 3H-PSGAG were achieved 2 hours post injection in all joints and that these concentrations were within the therapeutic range for PSGAG. The peak concentrations were not significantly different among the joints except between the antebrachiocarpal and the metacarpophalangeal joints. The areas under the concentration-time curves (AUC) for each joint were computed by the trapezoidal method from hour 0 through hour 24 and by empirical exponential decay beyond hour 24. These values were subjected to an analysis of variance (ANOVA). The overall multivariate test of AUC among all joints was not significant.The data from this study indicate that a single intramuscular 500 mg injection of PSGAG provided therapeutic levels of the drug in the equine antebrachiocarpal, metacarpophalangeal, tibiotarsal, and coronopedal joints within 2 hours of injection. While there were differences in levels between joints at certain time points, the AUC values suggest similar distribution of the drug in all joints tested. 相似文献
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Five healthy adult dogs were given a single IV dose (40 mg/kg of body weight) of ticarcillin disodium. Serum concentrations were measured serially over a period of 12 hours. Five days later, the drug was administered IM to the dogs at the same dose rate, and serum concentrations were measured serially for 12 hours. The mean peak serum concentration after IM administration was 120.5 micrograms/ml at 1.5 hours. Pharmacokinetic values following IV administration were (i) elimination rate constant = 0.8/hour-1, (ii) half-life = 0.8 hour, (iii) serum clearance = 292 ml/hr/kg, and (iv) apparent volume of distribution = 347 ml/kg. Estimated values after IM administration were (i) elimination rate constant = 0.6/hour, (ii) half-life = 1.1 hours, (iii) serum clearance = 218 ml/hr/kg, and (iv) apparent volume of distribution = 345 ml/kg; only the elimination rate constants were significantly different between the 2 routes of administration. 相似文献
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K J Whithair T L Bowersock W E Blevins J F Fessler M R White D C Van Sickle 《Veterinary surgery : VS》1992,21(5):367-373
Septic arthritis was induced in one antebrachiocarpal joint of seven horses by the intra-articular injection of 1 mL Staphylococcus aureus suspension containing a mean of 10(5) colony-forming units. Twenty-four hours after inoculation, four horses were treated by regional perfusion with 1 g of gentamicin sulfate, and three horses received 2.2 mg/kg gentamicin sulfate intravenously (IV) every 6 hours. Synovial fluid was collected for culture and cytology at regular intervals, and the synovial membranes were collected for culture and histologic examination at euthanasia 24 hours after the first treatment. Gentamicin concentration in the septic synovial fluid after three successful perfusions was 221.2 +/- 71.4 (SD) micrograms/mL; after gentamicin IV, it was 7.6 +/- 1.6 (SD) micrograms/mL. The mean leukocyte count in the inoculated joints decreased significantly by hour 24 in the successfully perfused joints. Terminal bacterial cultures of synovial fluid and synovial membranes were negative in two horses with successfully perfused joints. S. aureus was isolated from the infected joints in all three horses treated with gentamicin IV. 相似文献
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Transdermal absorption of four lidocaine (L) patches (5%) was compared with the transdermal absorption of L cream (5%) to evaluate the pharmacokinetics of the two formulations applied on the same anatomic region under dressing in eight horses. The animals were also assessed for antinociceptive effect after removal of the patches and cream, using a psychophysical method visual analog scale, by pricking the patient's skin to test the response to pain. Horses were randomly assigned to four treatment groups: in groups I and II, four L patches were applied for a period of 24 hours with and without alcohol precleaning, respectively; in group III, 5% L cream was applied every 2 hours over a 24-hour period on the same anatomic site. Group IV was the control. No clinical side effects were noted with either formulation. L was detectable in plasma 6 to 24 hours after application of the patches, and the highest plasma concentrations were reached between 12 and 18 hours. The use of alcohol to preclean the skin appeared to reduce the transdermal drug absorption over time. After L cream application, the peak plasma drug concentration occurred at 24 hours. Nociception assessment after L patch or L cream application showed a decreased response when the L cream was used. The results of this study showed that there was minimal absorption from the L patches compared with the L cream in horses. Also, the L cream treatment reduced significantly the intensity of nociception quality as measured by the visual analog scale. 相似文献
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OBJECTIVE: To investigate penetration of a topically applied nonsteroidal anti-inflammatory drug (NSAID) into tissues and synovial fluid. ANIMALS: 5 Greyhounds. PROCEDURE: Dogs were anesthetized and microdialysis probes placed in the dermis and gluteal muscle over each coxofemoral (hip) joint. Methylsalicylate (MeSA) was applied topically over the left hip joint. Dialysate and plasma (blood samples from the cephalic and femoral veins) were obtained during the subsequent 5 hours. Dogs were euthanatized, and tissue samples and synovial fluid were collected and analyzed for salicylic acid (SA) and MeSA by use of high-pressure liquid chromatography. RESULTS: SA and MeSA concentrations increased rapidly (< 30 minutes after application) in dialysate obtained from treated dermis. Salicylic acid also appeared in plasma within 30 minutes and reached a plateau concentration after 2 hours, although combined drug concentrations (SA plus MeSA) in plasma obtained from femoral vein samples were twice those measured in plasma obtained from the cephalic vein (SA only). Treated muscle had a progressive decrease in NSAID concentration with increasing depth (SA and MeSA), but it was significantly higher than the concentration in untreated muscle. Substantial amounts of SA and MeSA were also measured in synovial fluid of treated joints. CONCLUSIONS AND CLINICAL RELEVANCE: Topically applied NSAIDs can penetrate deeply into tissues and synovial fluid. Local concentrations higher than circulating systemic concentrations are suggestive that direct diffusion and local blood redistribution are contributing to this effect. Systemic blood concentrations may be inadequate to describe regional kinetics of topically applied drugs. 相似文献
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Daniel J. Burba DVM Michael A. Collier DVM Lawrence E. Default PhD Olivia Hanson-Painton PhD Harold C. Thompson Jr. Claude L. Holder 《Journal of Equine Veterinary Science》1993,13(12):696-703
The uptake and distribution of intramuscularly (IM) administered tritium-labeled polysulfated glycosaminoglycan (3H-PSGAG) in serum, synovial fluid, and articular cartilage of eight horses was quantitated, and hyaluronic acid (HA) concentration of the middle carpal joint was evaluated in a pharmacokinetic study. A full-thickness articular cartilage defect, created on the distal articular surface of the left radial carpal bone of each horse served as an osteochondral defect model. 3H-PSGAG (500 mg) was injected IM, between 14 and 35 days after creation of the defects. Scintillation analysis of serum and synovial fluid, collected from both middle carpal joints at specific predetermined times up to 96 hours post-injection, revealed mean 3H-PSGAG concentrations peaked at 2 hours post-injection. 3H-PSGAG was detected in cartilage and subchondral bone 96 hours post-injection in samples from all eight horses. There were no statistically significant differences in 3H-PSGAG concentration of synovial fluid or cartilage between cartilage defect and control (right middle carpal) joints.
HA assay of synovial fluid revealed concentrations significantly increased at 24, 48, and 96 hours post-injection in both joints. The concentration nearly doubled 48 hours post-injection. However, no statistically significant differences were found between synovial concentrations of HA in cartilage defect and control joints.
3H-PSGAG administered IM to horses, was distributed in the blood, synovial fluid, and articular cartilage. HA concentrations in synovial fluid increased after IM administration of polysulfated glycosaminoglycan. 相似文献
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Johnson RJ Black WD Sigler RE Baragi VM Gough AW 《American journal of veterinary research》2000,61(11):1396-1402
OBJECTIVE: To compare toxicokinetic variables and associated tissue drug concentrations with severity of articular lesions in weight-bearing joints of juvenile rabbits after oral administration of a fluoroquinolone. ANIMAL: Ten 6- to 7-week-old, 800- to 1,200-g, New Zealand White rabbits. PROCEDURES: Rabbits were gavaged daily with the fluoroquinolone PD 117596 at 500 mg/kg of body weight for 5 days. Blood samples were collected on day 4 at preestablished times, up to 24 hours after drug administration. On day 5 gross lesion severity and prevalence were evaluated in the major weight-bearing joints, and tissue specimens were collected (60 minutes after drug administration). Serum and tissue drug concentrations were determined by microbiologic plate assay. RESULTS: Macroscopically, treatment rabbits had a high prevalence of arthropathy with the distal portion of the femur having the highest prevalence and severity of lesions. Grossly, alterations to articular cartilage included 1 to 4 mm in diameter vesicles or erosions. Histologically, vesicles were identified in the midzone or close to the zone of calcified cartilage of treatment rabbits. Chondrocyte cellularity was reduced in affected areas, and perivesicular regions had reduced staining with Safranin O. Correlation analysis of area under the curve values with total scores for lesion severity had a significant positive relationship. CONCLUSIONS: Our findings support the use of juvenile rabbits as a model for arthropathic changes induced by fluoroquinolone administration. 相似文献
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Ivester KM Adams SB Moore GE Van Sickle DC Lescun TB 《American journal of veterinary research》2006,67(9):1519-1526
OBJECTIVE: To determine synovial fluid gentamicin concentrations and evaluate adverse effects on the synovial membrane and articular cartilage of tarsocrural joints after implantation of a gentamicin-impregnated collagen sponge. ANIMALS: 6 healthy adult mares. PROCEDURES: A purified bovine type I collagen sponge impregnated with 130 mg of gentamicin was implanted in the plantarolateral pouch of 1 tarsocrural joint of each horse, with the contralateral joint used as a sham-operated control joint. Gentamicin concentrations in synovial fluid and serum were determined for 120 hours after implantation by use of a fluorescence polarization immunoassay. Synovial membrane and cartilage specimens were collected 120 hours after implantation and evaluated histologically. RESULTS: Median peak synovial fluid gentamicin concentration of 168.9 microg/mL (range, 115.6 to 332 microg/mL) was achieved 3 hours after implantation. Synovial fluid gentamicin concentrations were < 4 microg/mL by 48 hours. Major histologic differences were not observed in the synovial membrane between control joints and joints implanted with gentamicin-impregnated sponges. Safranin-O fast green stain was not reduced in cartilage specimens obtained from treated joints, compared with those from control joints. CONCLUSIONS AND CLINICAL RELEVANCE: Implantation of a gentamicin-impregnated collagen sponge in the tarsocrural joint of horses resulted in rapid release of gentamicin, with peak concentrations > 20 times the minimum inhibitory concentration reported for common pathogens that infect horses. A rapid decrease in synovial fluid gentamicin concentrations was detected. The purified bovine type I collagen sponges did not elicit substantial inflammation in the synovial membrane or cause mechanical trauma to the articular cartilage. 相似文献
13.
A L Bertone C W McIlwraith R L Jones R W Norrdin M J Radin J L Lebel 《American journal of veterinary research》1987,48(3):519-529
To evaluate the effects of 5 treatments on clinical responses, synovial fluid analysis, radiographic changes, bacteriologic culture results of the synovial fluid and synovial membrane, microscopic characteristics of the synovial membrane, and articular cartilage histochemistry, Staphylococcus aureus organisms (1.6 X 10(6) colony-forming units) were inoculated into the tarsocrural joints of 12 horses (n = 24 joints; 2 joints/horse). Each horse was given phenylbutazone (2 g) orally, every 24 hours, beginning 24 hours after inoculation. Two horses (ie, 4 joints) were not given other treatment (controls; group 1). All other horses (ie, 20 joints) were given a trimethoprim-sulfadiazine combination orally, once daily (30 mg/kg; 8 joints) or twice daily (30 mg/kg q 12 hr; 12 joints). Each of these 20 joints were assigned to 1 of 5 treatment groups (4 joints/group) in a balanced incomplete block design. Group 2 (4 joints) was given only the antibiotics once daily. Twelve joints were treated by through-and-through joint lavage on day 1 (group 3), days 1 and 3 (group 4), or days 1, 3, and 6 (group 5). Joints in group 6 had an arthrotomy performed on day 1, with subsequent lavage via an indwelling drain every 12 hours for 4 days. In groups 3 through 6, 1 joint in each group was treated with antibiotics once daily, and 3 joints were treated with antibiotics twice daily. All horses were clinically assessed each day. Complete blood count was performed on days 3, 6, 10, and 21. Before inoculation and on days 0, 1, 3, 6, 10, and 21, synovial fluid specimens were collected and analyzed for color, clarity, total protein concentration, WBC count, differential count, and mucin clot-forming ability. Synovial fluid specimens were cultured bacteriologically before inoculation and on days 0 and 21. Horses in group 1 (controls) were euthanatized before day 6. All other horses were euthanatized on day 21. Tarsocrural joints were opened and examined. Synovial membrane specimens were bacteriologically cultured. Synovial membrane specimens were examined histologically (hemotoxylin and eosin stain) and articular cartilage specimens were (safranin O fast green stain) evaluated histochemically. Synovial membrane specimens were histologically graded into 5 categories. Intensity of articular cartilage intercellular staining with safranin 0 was graded for superficial, outer intermediate, inner intermediate, and deep zones. Two-way analysis of variance was performed to evaluate differences among groups and across time for the determinants evaluated.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
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H O Pohlenz-Zertuche M P Brown R Gronwall G A Kunkle K Merritt 《American journal of veterinary research》1992,53(7):1273-1276
Six healthy adult mixed breed dogs were each given 5 oral doses of trimethoprim (TMP)/sulfadiazine (SDZ) at 2 dosage regimens: 5 mg of TMP/kg of body weight and 25 mg of SDZ/kg every 24 hours (experiment 1) and every 12 hours (experiment 2). Serum and skin concentrations of each drug were measured serially throughout each experiment and mean serum concentrations of TMP and SDZ were determined for each drug for 24 hours (experiment 1) and 12 hours (experiment 2) after the last dose was given. In experiment 1, mean serum TMP concentration was 0.67 +/- 0.02 micrograms/ml, and mean skin TMP concentration was 1.54 +/- 0.40 micrograms/g. Mean serum SDZ concentration was 51.1 +/- 12.2 micrograms/ml and mean skin SDZ concentration was 59.3 +/- 9.8 micrograms/g. In experiment 2, mean serum TMP concentration was 1.24 +/- 0.35 micrograms/ml and mean skin TMP concentration was 3.03 +/- 0.54 micrograms/g. Mean serum SDZ concentration was 51.6 +/- 9.3 micrograms/ml and mean skin SDZ concentration was 71.1 +/- 8.2 micrograms/g. After the 5th oral dose in both experiments, mean concentration of TMP and SDZ in serum and skin exceeded reported minimal inhibitory concentrations of TMP/SDZ (less than or equal to 0.25/4.75 micrograms/ml) for coagulase-positive Staphylococcus sp. It was concluded that therapeutically effective concentrations in serum and skin were achieved and maintained when using the manufacturer's recommended dosage of 30 mg of TMP/SDZ/kg (5 mg of TMP/kg and 25 mg of SDZ/kg) every 24 hours. 相似文献
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Plasma cortisol response to ketoconazole administration in dogs with hyperadrenocorticism 总被引:1,自引:0,他引:1
E C Feldman D S Bruyette R W Nelson T B Farver 《Journal of the American Veterinary Medical Association》1990,197(1):71-78
The effect of orally administered ketoconazole on plasma cortisol concentration in dogs with hyperadrenocorticism was evaluated. Every 30 minutes from 0800 hours through 1600 hours and again at 1800 hours, 2000 hours, and 0800 hours the following morning, 15 clinically normal dogs and 49 dogs with hyperadrenocorticism had plasma samples obtained and analyzed for cortisol concentration. The mean (+/- SD) plasma cortisol concentration for the initial 8-hour testing period was highest in 18 dogs with adrenocortical tumor (5.3 +/- 1.6 micrograms/dl), lowest in 15 control dogs (1.3 +/- 0.5 micrograms/dl), and intermediate in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH; 3.4 +/- 1.2 micrograms/dl). Results in each of the 2 groups of dogs with hyperadrenocorticism were significantly (P less than 0.05) different from results in control dogs, but not from each other. The same cortisol secretory experiment was performed, using 8 dogs with hyperadrenocorticism (5 with PDH; 3 with adrenocortical tumor) before and after administration at 0800 hours of 15 mg of ketoconazole/kg of body weight. Significant (P less than 0.05) decrease in the 8-hour mean plasma cortisol concentration (0.9 +/- 0.2 microgram/dl) was observed, with return to baseline plasma cortisol concentration 24 hours later. Twenty dogs with hyperadrenocorticism (11 with PDH, 9 with adrenocortical tumor) were treated with ketoconazole at a dosage of 15 mg/kg given every 12 hours for a half month to 12 months. The disease in 2 dogs with PDH failed to respond to treatment, but 18 dogs had complete resolution of clinical signs of hyperadrenocorticism and significant (P less than 0.05) reduction in plasma cortisol responsiveness to exogenous adrenocorticotropin (ACTH).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
16.
Hogan DF Andrews DA Green HW Talbott KK Ward MP Calloway BM 《Journal of the American Veterinary Medical Association》2004,225(9):1406-1411
OBJECTIVE: To evaluate antiplatelet effects and pharmacodynamics of clopidogrel in cats. DESIGN: Original study. ANIMALS: 5 purpose-bred domestic cats. PROCEDURE: Clopidogrel was administered at dosages of 75 mg, p.o., every 24 hours for 10 days; 37.5 mg, p.o., every 24 hours for 10 days; and 18.75 mg, p.o., every 24 hours for 7 days. In all cats, treatments were administered in this order, with at least 2 weeks between treatments. Platelet aggregation in response to ADP and collagen and oral mucosal bleeding times (OMBTs) were measured before and 3, 7, and 10 days (75 and 37.5 mg) or 7 days (18.75 mg) after initiation of drug administration. Serotonin concentration in plasma following stimulation of platelets with ADP or collagen was measured before and on the last day of drug administration. Platelet aggregation, OMBT, and serotonin concentration were evaluated at various times after drug administration was discontinued to determine when drug effects were lost. RESULTS: For all 3 dosages, platelet aggregation in response to ADP platelet aggregation in response to collagen, and serotonin concentration were significantly reduced and OMBT was significantly increased at all measurement times during drug administration periods. All values returned to baseline values by 7 days after drug administration was discontinued. No significant differences were identified between doses. None of the cats developed adverse effects associated with drug administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of clopidogrel at dosages ranging from 18.75 to 75 mg, p.o., every 24 hours, results in significant antiplatelet effects in cats. 相似文献
17.
Oxytetracycline pharmacokinetics, tissue depletion, and toxicity after administration of a long-acting preparation at double the label dosage 总被引:1,自引:0,他引:1
Oxytetracycline (OTC) concentration in plasma and tissues, plasma pharmacokinetics, depletion from tissue, and toxicity were studied in 30 healthy calves after IM administration of a long-acting OTC preparation (40 mg/kg of body weight) at double the label dosage (20 mg/kg). Plasma OTC concentration increased rapidly after drug administration, and by 2 hours, mean (+/- SD) values were 7.4 +/- 2.6 micrograms/ml, Peak plasma OTC concentration was 9.6 +/- 2.6 micrograms/ml, and the time to peak plasma concentration was 7.6 +/- 4.0 hours. Plasma OTC concentration decreased slowly for 168 hours (elimination phase) after drug administration, and the elimination half-life was 23.9 hours. Plasma OTC concentration exceeded 3.8 micrograms/ml at 48 hours after drug administration. From 168 to 240 hours after drug administration, plasma OTC concentration decreased at a slower rate than that seen during the elimination phase. This slower phase was termed the depletion phase, and the depletion half-life was 280.7 hours. Tissue OTC concentration was highest in kidneys and liver. Lung OTC concentration exceeded 4.4 micrograms/g of tissue and 2.0 micrograms/g of tissue at 12 and 48 hours after drug administration, respectively. The drug persisted the longest in kidneys and liver. At 42 days after drug administration, 0.1 micrograms of OTC/g of kidney was detected. At 49 days after drug administration, all OTC tissue concentrations were below the detectable limit. Reactions and toxicosis after drug administration were limited to an anaphylaxis-like reaction (n = 1) and injection site swellings (n = 2). 相似文献
18.
OBJECTIVES: To measure serum polymyxin B concentration after single and repeated IV infusions in horses. ANIMALS: 5 healthy horses. PROCEDURES: In study 1, 1 mg (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24 hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5 treatments and blood samples were collected until 24 hours after the last dose. Polymyxin B concentration was measured as the ability to suppress nitrite production by murine macrophages stimulated with lipopolysaccharide and interferon-alpha. Urine was collected prior to the first drug infusion and 24 hours after the fifth drug infusion for determination of urinary gamma-glutamyl transferase (GGT)-to-creatinine ratios. RESULTS: In study 1, mean +/- SEM maximal serum polymyxin B concentration was 2.93 +/- 0.38 microg/mL. Polymyxin B was undetectable 18 hours after infusion. In study 2, maximal polymyxin B concentrations after the first and fifth doses were 2.98 +/- 0.81 microg/mL and 1.91 +/- 0.50 microg/mL, respectively. Mean trough concentration for all doses was 0.22 +/- 0.01 microg/mL. A significant effect of repeated administration on peak and trough serum concentration was not detected. Urine GGT-to-creatinine ratios were not affected by polymyxin B administration. CONCLUSIONS AND CLINICAL RELEVANCE: Polymyxin B given as multiple infusions to healthy horses by use of this protocol did not accumulate in the vascular compartment and appeared safe. Results support repeated IV use of 1 mg of polymyxin B/kg at 8-hour intervals as treatment for endotoxemia. 相似文献
19.
D R Gross W G Kramer F McCord C Wagner-Mann 《American journal of veterinary research》1986,47(9):2053-2056
Eight goats, 2 nontreated controls and 6 treated, were used to study the pharmacodynamics and pharmacokinetics of bishydroxycoumarin. In 5 of the 6 treated goats, there was a significant relationship between prothrombin times and drug concentrations. Activated clotting times did not change with time in either the controls or the treated goats. Five of 6 treated goats reached a plateau of drug concentration after 24 to 36 hours. Lag times for onset of pharmacologic effect ranged from 12 to 24 hours. The one goat (No. 3) that did not respond in concert with the other 5 was extremely nervous and became anorectic during the period of indoor confinement. 相似文献
20.
Serum and synovial fluid steady-state concentrations of trimethoprim and sulfadiazine in horses with experimentally induced infectious arthritis 总被引:1,自引:0,他引:1
The tarsocrural joints of 11 horses were inoculated with 1.2 to 2.16 x 10(6) viable Staphylococcus aureus organisms susceptible to a trimethoprim-sulfadiazine (TMP-SDZ) combination with minimal inhibitory concentration (MIC) of 0.25 micrograms of TMP/ml and 4.75 micrograms of SDZ/ml. Antimicrobial treatment consisted of oral administration of a TMP-SDZ combination--30 mg/kg of body weight given once daily (group-1 horses) or 60 mg/kg given as 30 mg/kg every 12 hours (group-2 horses). Paired serum and synovial fluid samples were obtained before intra-articular inoculation with the S aureus, after inoculation with S aureus but before antimicrobial treatment, and after inoculation at various hourly intervals after oral administration of the TMP-SDZ combination. The TMP-SDZ combination was administered daily in the 2 dosages for 21 days. Samples were collected after day 3 of repetitive drug administration so that drug steady-state concentration would have been achieved. Serum and synovial fluid samples were analyzed for TMP and SDZ concentrations. Administration of the TMP-SDZ combination at a dosage of 30 mg/kg once daily was not effective in maintaining TMP or SDZ concentrations above the MIC of TMP-SDZ for the S aureus (0.25 and 4.75 micrograms/ml for TMP and SDZ, respectively) in the infected synovial fluid or in maintaining adequate TMP concentration in the serum. The alternative use of the TMP-SDZ combination at a dosage of 60 mg/kg given as 30 mg/kg every 12 hours was effective in maintaining serum and synovial fluid concentrations of TMP and SDZ that were greater than the MIC for the infective organism.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献