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1.
Moore, S.A., Muñana, K.R., Papich, M.G., Nettifee‐Osborne, J.A. The pharmacokinetics of levetiracetam in healthy dogs concurrently receiving phenobarbital. J. vet. Pharmacol. Therap. 34 , 31–34. Levetiracetam (LEV) is a commonly used add‐on medication in dogs with refractory epilepsy. The objective of this study was to determine if the pharmacokinetics of LEV are altered by concurrent administration of phenobarbital (PB). Six healthy dogs received a single oral dose of LEV (16.7–27.8 mg/kg). Blood samples were collected at baseline and intermittently for 24 h. The study was repeated after the dogs received oral PB (2.0–3.3 mg/kg) twice daily for 21 days. Plasma LEV levels were evaluated by high pressure liquid chromatography, and data analyzed using a compartmental model. Compared with values determined when LEV was administered alone, concurrent administration of PB resulted in a decrease in LEV peak concentration (Cmax) from 32.39 ± 6.76 to 18.22 ± 8.97 (P = 0.0071), a decrease in elimination half‐life (T1/2) from 3.43 ± 0.47 to 1.73 ± 0.22 (P = 0.0005), and an increase in oral clearance from 124.93 ± 26.93 to 252.99 ± 135.43 ml/h/kg (P < 0.0001). Concurrent PB administration significantly alters the pharmacokinetics of LEV in the dog, indicating that dosage adjustments might be necessary when the drug is administered with PB.  相似文献   

2.
Pimobendan is a benzimidazole‐pyridazinone derivative, marketed as a racemic mixture for the management of canine heart failure. Pharmacokinetics of the enantiomers of pimobendan and its oral bioavailability have not been described in dogs. The aim of this study was to describe pharmacokinetics of three formulations of pimobendan in healthy dogs: the licensed capsule product, and novel liquid and intravenous formulations. A three‐period, nested randomized two‐treatment crossover design was used. Pimobendan was administered p.o. at 0.25 and i.v. at 0.125 mg/kg. Blood and plasma samples were analysed by liquid chromatography–mass spectrometry. Noncompartmental modelling was used to describe the pharmacokinetics. Parameters were compared between formulations using a general linear model. Bioequivalence of the oral formulations was tested using CI90 for AUC(0–∞) and Cmax. Bioavailability of pimobendan after oral dosing was 70%. Liquid and capsule formulations were bioequivalent only for AUC. The positive enantiomer of pimobendan (PE) had a larger volume of distribution than the negative enantiomer (NE) (281 ± 48 vs. 215 ± 68 mL/kg; P = 0.003) and a shorter half‐life (21.7 vs. 29.9 min; P = 0.004). The NE was distributed more quickly than the PE into blood cells. Enantiomers of pimobendan have differing absorption, distribution and elimination. The pharmacokinetics of pimobendan in healthy dogs was described.  相似文献   

3.
The goal of the current study was to determine the efficacy of oral docetaxel in combination with cyclosporine in the treatment of canine epithelial cancer. Requirements for eligibility were histological confirmation of epithelial neoplasia, measurable disease, no chemotherapy treatment within 2 weeks, and a life expectancy of ≥3 months. Fifty‐one dogs were enrolled. All dogs received 1.625 mg kg?1 of docetaxel with 5 mg kg?1 of cyclosporine (DT/CSA) by gavage. Ten dogs had progressive disease at 2 weeks, one dog died, and one dog was withdrawn from the study. Thirty‐nine dogs were given a second dose of DT/CSA, three each receiving a third or fourth dose. Eight dogs had a dose reduction (1.5 mg kg?1) and six dogs had treatment delays primarily for gastrointestinal toxicity. The overall response rate was 16.7% (8/48 had a partial response there were no complete responses). The highest response rate was seen in dogs with oral squamous cell carcinoma (50%; 6/12).  相似文献   

4.
Wright, H. M., Chen, A. V., Martinez, S. E., Davies, N. M. Pharmacokinetics of oral rufinamide in dogs. J. vet. Pharmacol. Therap.  35 , 529–533. The objective of this study was to determine the pharmacokinetic properties and short‐term adverse effect profile of single‐dose oral rufinamide in healthy dogs. Six healthy adult dogs were included in the study. The pharmacokinetics of rufinamide were calculated following administration of a single mean oral dose of 20.0 mg/kg (range 18.6–20.8 mg/kg). Plasma rufinamide concentrations were determined using high‐performance liquid chromatography, and pharmacokinetic data were analyzed using commercial software. No adverse effects were observed. The mean terminal half‐life was 9.86 ± 4.77 h. The mean maximum plasma concentration was 19.6 ± 5.8 μg/mL, and the mean time to maximum plasma concentration was 9.33 ± 4.68 h. Mean clearance was 1.45 ± 0.70 L/h. The area under the curve (to infinity) was 411 ± 176 μg·h/mL. Results of this study suggest that rufinamide given orally at 20 mg/kg every 12 h in healthy dogs should result in a plasma concentration and half‐life sufficient to achieve the therapeutic level extrapolated from humans without short‐term adverse effects. Further investigation into the efficacy and long‐term safety of rufinamide in the treatment of canine epilepsy is warranted.  相似文献   

5.
Background: Hydration status is important to the cardiovascular system because of its effects on preload. Decreased preload can alter echocardiographic measurements of systolic and diastolic function, potentially confounding interpretation of results. Hypothesis/Objectives: Mild fluid deficits are associated with measurable echocardiographic changes that are validated by physical and biochemical markers of decreased intravascular volume. Animals: Twenty‐five healthy staff/student‐owned dogs with no evidence of cardiac or renal disease. Methods: Prospective, interventional laboratory study. Dogs were randomly assigned to water deprivation (WD) alone for 8 hours (n = 13) or to furosemide treatment (FTx, 2.5 mg/kg IV) followed by WD for 8 hours (n = 12). Echocardiograms, biochemical sampling, and physical parameters were measured at baseline, and after 4 and 8 hours. Results: Both protocols induced fluid deficit as indicated by significant (P < .00001) decreases in weight at 4 hours (WD, 1.1%; FTx, 3.7%) and 8 hours (WD, 2.7%; FTx, 4.5%). Furosemide significantly decreased left ventricular end‐diastolic volume (54.3 ± 19.3–42.1 ± 17.3 mL, P < .0001), cardiac index (4.2 ± 1.1–2.9 ± 0.9 L/min/M2, P < .0001), and mitral valve E wave velocity (0.79 ± 0.2–0.66 ± 0.2 m/s, P= .0004). These changes were accompanied by significant increases in blood urea nitrogen concentration (13.8 ± 2.6–14.8 ± 2.7 mg/dL, P= .04), vasopressin concentration (1.4 ± 1.2–3.3 ± 1.9 pg/mL, P= .045), and PCV (49.8 ± 4.5–53.2 ± 6.5%, P= .006). Effects of water deprivation alone were similar, but less pronounced. Conclusions and Clinical Importance: Mild fluid deficits have measurable hemodynamic effects in dogs. Hydration status should be considered when evaluating cardiac function by echocardiogram.  相似文献   

6.
In dogs, a mean broncho‐arterial ratio of 1.45 ± 0.21 has been previously defined as normal. These values were obtained in dogs under general inhalational anesthesia using a single breath‐hold technique. The purpose of the study was to determine whether ventilation technique and bronchial diameter have an effect on broncho‐arterial ratios. Four healthy Beagle dogs were scanned twice, each time with positive‐pressure inspiration and end expiration. For each ventilation technique, broncho‐arterial ratios were grouped into those obtained from small or large bronchi using the median diameter of the bronchi as the cutoff value. Mean broncho‐arterial ratios obtained using positive‐pressure inspiration (1.24 ± 0.23) were statistically greater than those obtained at end expiration (1.11 ± 0.20) P = 0.005. There was a strong positive correlation between bronchial diameter and broncho‐arterial ratios for both ventilation techniques (positive‐pressure inspiration rs = .786, P < 0.0005 and end expiration rs = .709, P < 0.0005). Mean broncho‐arterial ratio for the large bronchi obtained applying positive‐pressure inspiration was 1.39 cm ± 0.20 and during end expiration was 1.22 cm ± 0.20. Mean broncho‐arterial ratio for the small bronchi obtained during positive‐pressure inspiration was 1.08 cm ± 0.13 and during end expiration was 1.01 cm ± 0.13. There was a statistically significant difference between these groups (F = 248.60, P = 0.005). Findings indicated that reference values obtained using positive‐pressure inspiration or from the larger bronchi may not be applicable to dogs scanned during end expiration or to the smaller bronchi.  相似文献   

7.
The purpose of this study was to determine the pharmacokinetic interaction between ivermectin (0.4 mg/kg) and praziquantel (10 mg/kg) administered either alone or co‐administered to dogs after oral treatment. Twelve healthy cross‐bred dogs (weighing 18–21 kg, aged 1–3 years) were allocated randomly into two groups of six dogs (four females, two males) each. In first group, the tablet forms of praziquantel and ivermectin were administered using a crossover design with a 15‐day washout period, respectively. Second group received tablet form of ivermectin plus praziquantel. The plasma concentrations of ivermectin and praziquantel were determined by high‐performance liquid chromatography using a fluorescence and ultraviolet detector, respectively. The pharmacokinetic parameters of ivermectin following oral alone‐administration were as follows: elimination half‐life (t1/2λz) 110 ± 11.06 hr, area under the plasma concentration–time curve (AUC0–∞) 7,805 ± 1,768 hr.ng/ml, maximum concentration (Cmax) 137 ± 48.09 ng/ml, and time to reach Cmax (Tmax) 14.0 ± 4.90 hr. The pharmacokinetic parameters of praziquantel following oral alone‐administration were as follows: t1/2λz 7.39 ± 3.86 hr, AUC0–∞ 4,301 ± 1,253 hr.ng/ml, Cmax 897 ± 245 ng/ml, and Tmax 5.33 ± 0.82 hr. The pharmacokinetics of ivermectin and praziquantel were not changed, except Tmax of praziquantel in the combined group. In conclusion, the combined formulation of ivermectin and praziquantel can be preferred in the treatment and prevention of diseases caused by susceptible parasites in dogs because no pharmacokinetic interaction was determined between them.  相似文献   

8.
The objectives were to document the pharmacokinetics of intravenous, enteric‐coated oral and plain oral omeprazole in fasted horses and to investigate the impact of feeding on the bioavailability of an enteric‐coated omeprazole. Twelve horses received four treatments: intravenous omeprazole (0.5 mg/kg) in the fasted state (IV‐Fasted), enteric‐coated omeprazole (4 mg/kg) orally in the fasted state (ECO‐Fasted), enteric‐coated omeprazole (4 mg/kg) orally in the fed state (ECO‐Fed) and plain omeprazole (4 mg/kg) orally in the fasted state (PL‐Fasted). Plasma omeprazole concentrations were determined by UHPLC‐MS. Bioavailability was higher (P = 0.038) in the ECO‐Fasted group (21.5 [9.0–27.7]%) than the PL‐Fasted group (10.1 [7.7–13.3]%). Similarly, AUC0‐∞ was higher in the ECO‐Fasted group than the PL‐Fasted group (P = 0.027). No significant differences were present between the ECO‐Fasted and ECO‐Fed groups with regards to bioavailability, Cmax, Tmax or AUC0‐∞. When the half‐life data from the oral formulations was pooled, it was longer than that observed in the IV‐Fasted group (100 [73–118] min) and 35 [34‐39] min, respectively; P < 0.0001). Bioavailability of enteric‐coated omeprazole was higher than previously reported and feeding had minimal impact. Bioavailability of plain omeprazole was approximately half that of enteric‐coated omeprazole. The longer half‐life observed following oral administration was consistent with the flip‐flop effect and has not previously been described for omeprazole in the horse.  相似文献   

9.
Yancey, M. F., Merritt, D. A., Lesman, S. P., Boucher, J. F., Michels, G. M. Pharmacokinetic properties of toceranib phosphate (Palladia?, SU11654), a novel tyrosine kinase inhibitor, in laboratory dogs and dogs with mast cell tumors. J. vet. Pharmacol. Therap. 33 , 162–171. Toceranib phosphate (Palladia?, SU11654), an oral tyrosine‐kinase inhibitor, is under investigation for the treatment of mast cell tumors in dogs. The pharmacokinetics of toceranib phosphate has been characterized in dogs. Means of the following pharmacokinetic parameters were estimated following a 1.0 mg/kg i.v. dose to laboratory beagles: plasma clearance of 1.45 L/kg/h, volume of distribution of 29.7 L/kg, and terminal half‐life of 17.7 h. Following single oral doses of 3.25 mg/kg administered to laboratory beagles, mean Cmax estimates ranged from 68.6 ng/mL to 112 ng/mL with tmax ranging from 5.3 h and 9.3 h postdose. Terminal half‐life was estimated at 31 h. Oral bioavailability was 76.9%. There were no statistically significant (P > 0.05) differences with any pharmacokinetic parameter due to fed/fasted state or with time during 13 weeks of every‐other‐day dosing at 3.25 mg/kg. Toceranib concentrations were proportional with dose over the range of 2.0 to 6.0 mg/kg. The pharmacokinetics of toceranib in client‐owned dogs of a variety of pure and mixed breeds with mast cell tumors was similar to that in healthy laboratory dogs. In summary, toceranib phosphate exhibited moderate clearance, a high volume of distribution, and a moderate elimination half‐life. After a single oral dose at 3.25 mg/kg, the concentration vs. time curve showed broad, sustained exposure with measurable concentrations for more than 48 h. These pharmacokinetic parameters support every‐other‐day administration of toceranib phosphate at an initial dose of 3.25 mg/kg for the treatment of mast cell tumors in dogs.  相似文献   

10.
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11.
Cox, S.R., Lesman, S.P., Boucher, J.F., Krautmann, M.J., Hummel, B.D., Savides, M., Marsh, S., Fielder, A., Stegemann, M.R. The pharmacokinetics of mavacoxib, a long‐acting COX‐2 inhibitor, in young adult laboratory dogs. J. vet. Pharmacol. Therap. 33 , 461–470. The pharmacokinetics of mavacoxib were evaluated in an absolute bioavailability study, a dose‐proportionality study and a multi‐dose study in young healthy adult laboratory Beagle dogs and in a multi‐dose safety study in Beagle‐sized laboratory Mongrel dogs. When administered as the commercial tablet formulation at 4 mg/kg body weight (bw) to fasted dogs, the absolute bioavailability (F) of mavacoxib was 46.1%; F increased to 87.4% when mavacoxib was administered with food. Following intravenous administration, the total body plasma clearance of mavacoxib was 2.7 mL·h/kg, and the apparent volume of distribution at steady‐state was 1.6 L/kg. The plasma protein binding of mavacoxib was approximately 98% in various in vitro and ex vivo studies. The dose‐normalized area under the plasma concentration–time curve was similar in Beagle and Beagle‐sized Mongrel dogs when mavacoxib was administered with food. Mavacoxib exhibited dose‐proportional pharmacokinetics for single oral doses of 2–12 mg/kg in Beagle dogs and for multiple oral doses of 5–25 mg/kg in Beagle‐sized Mongrel dogs. Only minor accumulation occurred when mavacoxib was administered at doses of 2–25 mg/kg bw orally to laboratory dogs with a 2‐week interval between the 1st two doses but with a monthly interval thereafter. Across all three Beagle studies (n = 63) the median terminal elimination half‐life (t½) was 16.6 days, with individual values ranging 7.9–38.8 days. The prolonged t½ for mavacoxib supports the approved regimen in which doses are separated by 2–4 weeks.  相似文献   

12.
Background: The sodium‐calcium exchanger (NCX‐1), an established cardiac biomarker, was postulated previously as differentiating between heart failure (HF) and renal failure (RF) in dogs. The effect of azotemia on NCX‐1 expression has not been studied. Hypothesis: In contrast to other cardiac biomarkers (eg, N‐terminal‐proBNP), we hypothesized that the expression level of NCX‐1 is not influenced by either azotemia or decreased renal clearance. Animals: Fifteen client‐owned healthy control dogs, 14 dogs with chronic mitral valvular insufficiency (CMVI), classified based on severity of the disease by the established International Small Animal Cardiac Health Council classification system, and 15 dogs with RF, grouped according to the International Renal Interest Society stage classification. Methods: A comparative study of the expression levels of NCX‐1, evaluated in peripheral blood samples from dogs with HF, RF, and healthy controls by quantitative PCR. Results: NCX‐1 expression was significantly increased in moderate (2.99 ± 0.61 [fold changes relative to normal group]) to severe (4.35 ± 1.44) CMVI dogs (P < .01). In contrast, NCX‐1 expression was not increased in the azotemic dogs. Furthermore, there was also no correlation between increased concentrations of creatinine and urea nitrogen in serum and NCX‐1 expression in the RF group. Conclusions and Clinical Importance: Azotemia likely does not affect NCX‐1 expression.  相似文献   

13.
Background: Thrombelastography (TEG) and indicators of secondary and tertiary hemostasis might be altered in dogs with endotoxemia. Hypothesis: Endotoxemia influences measures of coagulation in dogs. Animals: Ten healthy cross‐bred dogs. Material and Methods: Prospective laboratory study between controls (n = 5) receiving 0.9% saline IV and the study group (n = 5) treated with low‐dose lipopolysaccharide (0.02 mg/kg IV). Physical examination and sampling for measurement of leukocytes, platelets, and coagulation variables were performed at time points 0, 1, 4, and 24 hours. Coagulation variables included kaolin‐activated TEG, 1‐stage prothrombin time (OSPT), activated partial thromboplastin time (aPTT), fibrinogen, factor VIII, antithrombin, protein C, protein S, activated protein C (APC)‐ratio calculated from aPTT with and without presence of APC), and D‐Dimers. Results: Endotoxemia‐induced clinical signs included lethargy (n = 5/5), diarrhea (n = 4/5), emesis (n = 4/5), and abdominal pain (2/5). After 1 hour there was severe leukopenia (2.5 ± 0.7 × 109/L; mean ± SD, P < .0001) and a 2.2‐fold increase in D‐Dimers (0.81 ± 0.64 mg/L, P < .0001). After 4 hours there was hyperthermia (40.3 ± 0.4°C, P < .0001) and increases in OSPT (10.5 ± 2.7 seconds, P < .0001), aPTT (16.7±5.2 seconds, P= 0.002). A significant decrease in fibrinogen (1.5±1.0 g/L, P= 0.001), protein C (31 ± 33%, P <.0001), protein S (63 ± 47%, P < .0001), TEG α (58 ± 19, P= .007), and TEG maximal amplitude (50 ± 19 mm, P= .003) was seen compared with the controls. APC‐ratio rose significantly (2.5 ± 0.2, P < .0001) without exceeding the reference interval (n = 4/5). Conclusion and Clinical Importance: D‐Dimers are the earliest indicator for endotoxemia‐associated coagulation abnormalities followed by decreased protein C concentration. APC‐ratio and TEG were not good screening variables.  相似文献   

14.
Recently, tramadol and its active metabolite, O‐desmethyltramadol (M1), have been studied as analgesic agents in various traditional veterinary species (e.g., dogs, cats, etc.). This study explores the pharmacokinetics of tramadol and M1 after intravenous (IV) and oral (PO) administration in rhesus macaques (Macaca mulatta), a nontraditional veterinary species. Rhesus macaques are Old World monkeys that are commonly used in biomedical research. Effects of tramadol administration to monkeys are unknown, and research veterinarians may avoid inclusion of this drug into pain management programs due to this limited knowledge. Four healthy, socially housed, adult male rhesus macaques (Macaca mulatta) were used in this study. Blood samples were collected prior to, and up to 10 h post‐tramadol administration. Serum tramadol and M1 were analyzed using liquid chromatography–mass spectrometry. Noncompartmental pharmacokinetic analysis was performed. Tramadol clearance was 24.5 (23.4–32.7) mL/min/kg. Terminal half‐life of tramadol was 111 (106–127) min IV and 133 (84.9–198) min PO. Bioavailability of tramadol was poor [3.47% (2.14–5.96%)]. Maximum serum concentration of M1 was 2.28 (1.88–2.73) ng/mL IV and 11.2 (9.37–14.9) ng/mL PO. Sedation and pruritus were observed after IV administration.  相似文献   

15.
This randomized controlled trial study aimed to identify the optimal positive pressure (PP) level that can clear atelectasis while avoiding pulmonary hyperinflation during the breath‐hold technique in dogs undergoing thoracic computed tomography (CT). Sixty dogs affected by mammary tumors undergoing thoracic CT for the screening of pulmonary metastases were randomly assigned to six groups with different levels of PP during the breath‐hold technique: 0 (control), 5 (PP5), 8 (PP8), 10 (PP10), 12 (PP12), and 15 (PP15) cmH2O. The percentage of atelectatic lung region was lower in the PP10 (3.7 ± 1.1%; P = 0.002), PP12 (3.4 ± 1.3%; P = 0.0001), and PP15 (2.8 ± 0.9%; P = 0.006) groups than in the control group (5.0 ± 2.3%), and the percentage of poorly aerated lung region was lower in the PP8 (15.1 ± 2.6%; P = 0.0009), PP10 (13.0 ± 2.0 %; P = 0.002), PP12 (13.0 ± 2.2 %; P = 0.0002), and PP15 (11.1 ± 1.9%; P = 0.0002) groups than in the control group (19.8 ± 5.0). The percentage of normally aerated lung region, however, was higher in the PP10 (79.7 ± 4.1%; P = 0.005), PP12 (79.8 ± 5.1%; P = 0.0002), and PP15 (80.2 ± 4.9%; P = 0.002) groups than in the control group (73.4 ± 6.6%). A PP of 10–12 cmH2O during the breath‐hold technique should be considered to improve lung aeration during a breath‐hold technique in dogs undergoing thoracic CT.  相似文献   

16.
Background: Satraplatin is the 1st orally bioavailable platinum anticancer drug. Objective: Our objectives were to evaluate efficacy in vitro against a canine cancer cell line, to determine the maximally tolerated dose (MTD) of satraplatin in tumor‐bearing dogs, to identify the dose‐limiting and other toxicities in dogs, and to record pharmacokinetics (PK). Animals: Dogs with macro‐ or microscopic malignant neoplasia. Methods: D17 canine osteosarcoma cells first were evaluated in a clonogenic survival assay. Then, dogs with a diagnosis of malignant neoplasia were prospectively entered in standard 3 + 3 cohorts. Additional patients were entered at the MTD to assess efficacy. Total and free platinum (by ultrafiltrate) concentrations were determined with inductively coupled plasma mass spectroscopy. Results: Satraplatin inhibited clonogenic survival in vitro at clinically relevant and achievable concentrations. Twenty‐three dogs were treated, 14 with PK evaluation. The MTD was 35 mg/m2/d for 5 days, repeated every 3–4 weeks. Bioavailability was 41%. PK variables (mean ± SD) at the MTD included Tmax 1.8 (± 0.7) hours, Cmax 72 (± 26) ng/mL, area under concentration (AUC)0–24 h 316 (± 63) h × ng/mL, and MRT 7 (± 1.3) hours. Higher AUC after the 5th versus the 1st dose suggested drug accumulation. Interestingly, platelets consistently reached nadir sooner than did neutrophils (day 14 versus 19). Myelosuppression was dose‐limiting and gastrointestinal toxicity was mild. Conclusions and Clinical Importance: Satraplatin was well tolerated in tumor‐bearing dogs, thus warranting further investigation in a phase II trial.  相似文献   

17.
Objective To determine the effects of 0.005% latanoprost and 2% dorzolamide/0.5% timolol on the blood‐aqueous barrier (BAB) in normal dogs. Animals studied Eight mixed‐breed and pure‐breed dogs. Procedures Baseline anterior chamber fluorophotometry was performed on eight normal dogs. Sodium fluorescein was injected and the dogs were scanned 60–90 min post‐injection. Seventy‐two hours following the baseline scan, one eye received one drop of latanoprost. Fluorophotometry was repeated 4 h after drug administration. Following a washout period, the identical procedure was performed 4 h after the administration of dorzolamide/timolol. The degree of BAB breakdown was determined by comparing the concentrations of fluorescein within the anterior chamber before and after drug administration. BAB breakdown was expressed as a percentage increase in the post‐treatment fluorescein concentration over the baseline concentration: %INC [Fl] = {([Fl]post – [Fl]baseline)/[Fl]baseline} × 100. The percentage increase in fluorescein concentration in the treated eye was compared to that in the nontreated eye using a paired t‐test with significance set at P ≤ 0.05. Results Following administration of latanoprost, the fluorescein in the treated eyes increased 49% (± 58%) from baseline compared to 10% (± 31%) in the untreated eyes (P = 0.016). Following administration of dorzolamide/timolol, the fluorescein concentration increased 38% (± 54%) compared to baseline vs. 24% (± 38%) in the untreated eyes (P = 0.22). Conclusions The results of this study show that topical latanoprost may cause BAB disruption in normal dogs while topical dorzolamide/timolol may have no effect on the BAB in normal dogs.  相似文献   

18.
Background: Cyclophosphamide is an alkylating chemotherapeutic drug administered IV or PO. It is currently assumed that exposure to the active metabolite, 4‐hydroxycyclophosphamide (4‐OHCP), is the same with either route of administration.

Objectives:

To characterize the pharmacokinetics of cyclophosphamide and 4‐OHCP in dogs with lymphoma when administered PO or IV. Animals: Sixteen client‐owned dogs with substage A lymphoma were enrolled in the study. Eight dogs received cyclophosphamide IV and 8 received it PO. Methods: Prospective randomized clinical trial was performed. Blood was collected from each dog at specific time points after administration of cyclophosphamide. The serum was evaluated for the concentration of cyclophosphamide and 4‐OHCP with mass spectrometry and liquid chromatography. Results: Drug exposure to cyclophosphamide measured by area under the curve (AUC)0–inf is significantly higher after intravenous administration (7.14 ± 3.77 μg/h/mL) compared with exposure after oral administration (P‐value < .05). No difference in drug exposure to 4‐OHCP was detected after IV (1.66 ± 0.36 μg/h/mL) or PO (1.42 ± 0.64 μg/h/mL) administered cyclophosphamide. Conclusions and Clinical Importance: Drug exposure to the active metabolite 4‐OHCP is equivalent after administration of cyclophosphamide either PO or IV.  相似文献   

19.
Objective: To evaluate plasma sodium and glucose concentrations in dogs with congestive heart failure (CHF) prior to treatment and evaluate the differences between survivors and non‐survivors. Design: Retrospective study. Animals: Fifty‐nine dogs with CHF prior to receiving cardiac medication. Interventions: None. Measurements and main results: The mean plasma sodium concentration in dogs with CHF was below the reference range (144–156 mmol/L) and significantly lower (P=0.009) in non‐survivors (141±6 mmol/L) compared with survivors (147±4 mmol/L). The mean plasma glucose concentration was above the reference range (76–117 mg/dL) and significantly higher (P=0.004) in non‐survivors (128±52 mg/dL) compared with survivors (100±13 mg/dL). Forty‐four percent of non‐survivors had concurrent low plasma sodium and high plasma glucose concentrations, whereas no survivors had both abnormalities (P<0.0001). Conclusions: Lower plasma sodium and higher plasma glucose are associated with a worse outcome in dogs with CHF.  相似文献   

20.
Background: Despite many epidemiological reports concerning the efficacy of angiotensin‐converting enzyme (ACE) inhibitors in dogs with mitral regurgitation (MR), the hemodynamic effects of ACE inhibitor administration have not been fully evaluated. Objectives: To document left atrial pressure (LAP) in dogs with MR administered ACE inhibitors, in order to obtain interesting information about daily LAP changes with administration of ACE inhibitors. Animals: Five healthy Beagle dogs weighing 9.8 to 14.2 kg (2 males and 3 females; aged 2 years). Methods: Experimental, crossover, and interventional study. Chordae tendineae rupture was induced, and a radiotelemetry transmitter catheter was inserted into the left atrium. LAP was recorded for 72 consecutive hours during which each of 3 ACE inhibitors—enalapril (0.5 mg/kg/d), temocapril (0.1 mg/kg/d), and alacepril (3.0 mg/kg/d)—were administered in a crossover study. Results: Averaged diurnal LAP was significantly, but slightly reduced by alacepril (P= .03, 19.03 ± 3.01–18.24 ± 3.07 mmHg). The nightly drops in LAP caused by alacepril and enalapril were significantly higher than the daily drops (P= .03, ?0.98 ± 0.19 to ?0.07 ± 0.25 mmHg, and P= .03, ?0.54 ± 0.21–0.02 ± 0.17 mmHg, respectively), despite the fact that the oral administrations were given in the morning. Systolic blood pressure (122.7 ± 14.4–117.4 ± 13.1 mmHg, P= .04) and systemic vascular resistance (5800 ± 2685–5144 ± 2077 dyne × s/cm5, P= .03) were decreased by ACE inhibitors. Conclusions and Clinical Importance: ACE inhibitors decrease LAP minimally, despite reductions in left ventricular afterload. ACE inhibitors should not be used to decrease LAP.  相似文献   

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