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1.
Atrial fibrillation (AF) was induced in anesthetized Beagle hounds to determine the dose of diltiazem (D) that resulted in hemodynamic function similar to that observed during sinus rhythm (SR). Dogs were instrumented to record hemodynamic and electrophysiological parameters. Six dogs were given D, IV at cumulative doses of 0.063, 0.188, 0.438, 0.938, and 1.938 mg/kg, whereas 6 other dogs received vehicle in equivalent volumes. Plasma concentrations (PC) of D were measured. A cumulative dose of D between 0.438 and 0.938 mg/kg produced PC of 67.8 to 117.4 ng/mL and resulted in a heart rate (HR) closest to that observed during SR. At doses up to 0.938 mg/kg, no parameter of systolic function fell below that obtained during SR. At a dose of 0.938 mg/kg, the left ventricular end-diastolic and right atrial pressures exceeded those during SR. The rate-pressure product did not differ from that during SR at a dose of 0.938 mg/kg and fell below that during SR at the dose of 1.938 mg/kg. Left ventricular efficiency decreased from SR to AF, returned to values not different from those during SR at a dose of 0.938 mg/kg, and increased to values above those observed during SR at a dose of 1.938 mg/kg. In AF, slowing the HR with 0.438-0.938 mg/kg of D with resultant PC of 67.8-117.4 ng/mL results in cardiovascular function not different from that observed during SR.  相似文献   

2.
The serum salicylate concentration produced by oral administration of plain aspirin and several aspirin-containing products given at 8-hour intervals for 7 treatments was measured in 36 laboratory-conditioned adult dogs. The dogs were randomly allotted to 6 groups of 6 dogs each: group 1 was given plain aspirin at a dosage of 25 mg/kg of body weight: group 2 was given plain aspirin at a dosage of 10 mg/kg; group 3 was given buffered aspirin at a dosage of 25 mg/kg; group 4 was given enteric-coated aspirin at a dosage of 25 mg/kg; group 5 was given buffered aspirin at a dosage of 25 mg/kg; and, group 6 was given a placebo. Serum salicylate concentration was measured at 2-hour intervals for the first 8 hours, and then at 8-hour intervals for the next 40 hours. Following the last dosing, serum salicylate concentration was measured at 2-hour intervals until 56 hours; the final 2 samples were measured at 64 and 72 hours. The effect of aspirin on the gastric mucosa was studied in 12 dogs, 3 each randomly selected from groups 1, 3, 4, and 5. The gastric mucosa of each dog was examined with a fiberoptic gastroscope 3 days before the beginning of treatment; lesions were not seen. The drugs were administered as described and the gastric mucosa of each dog was reexamined at 72 hours. Administration of the aspirin-containing products at 8-hour intervals resulted in sustained therapeutic serum salicylate concentrations (greater than 5 mg/dl) in all dogs, except those of group 2. The greatest fluctuation in serum salicylate concentration was found in dogs of group 4. Gastric lesions were seen only in the 3 dogs of group 1.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

3.
OBJECTIVE: To evaluate the effects of twice-daily oral administration of a low-dose of trilostane treatment and assess the duration of effects after once-daily trilostane administration in dogs with naturally occurring hyperadrenocorticism (NOH). DESIGN: Prospective study. ANIMALS: 28 dogs with NOH. PROCEDURES: 22 dogs received 0.5 to 2.5 mg of trilostane/kg (0.23 to 1.14 mg/lb) orally every 12 hours initially. At intervals, dogs were reevaluated; owner assessment of treatment response was recorded. To assess drug effect duration, 16 of the 22 dogs and 6 additional dogs underwent 2 ACTH stimulation tests 3 to 4 hours and 8 to 9 hours after once-daily trilostane administration. RESULTS: After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [3]). At 3 to 4 hours and 8 to 9 hours after once-daily dosing, mean post-ACTH stimulation serum cortisol concentrations were 2.60 and 8.09 Pg/dL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with NOH, administration of trilostane at low doses every 12 hours was effective, although 2 dogs became ill during treatment. Drug effects diminished within 8 to 9 hours. Because of potential adverse effects, lower doses should be evaluated.  相似文献   

4.
We investigated the effects of graded dosages of magnesium given i.v. to anesthetized dogs on blood pressure, cardiac output, and electrophysiology. Magnesium was infused at 0.12 mEq/kg/minute until ventricular fibrillation occurred naturally or was provoked by programmed electrical stimulation or until arrest of the sinuatrial node in 8 dogs. Plasma total magnesium concentrations doubled in 1 minute of that infusion rate, and a hemodynamically safe plasma concentration of 12.2 mEq/L was achieved after 16 minutes of infusion. Heart rate, inotropy, lusitropy, and cardiac output increased up to a cumulative infusion dosage of magnesium of 1.0-2.0 mEq/kg, which produced plasma magnesium concentrations of 8.5-12.2 mEq/L (n = 5). Above the cumulative infusion dosage, inotropy decreased and lusitropy increased until death occurred between cumulative infusion dosages of 5.9 mEq/kg and 10.9 mEq/kg. Arterial pressure and vascular resistance decreased, and PQ interval and QRS complex increased, in a dose-dependent fashion. The relationship between ionized and total magnesium was y = 0.624x - 0.542 (r2 = .986), where y is ionized and x is total magnesium in mEq/L in 3 dogs. In conclusion, a cumulative infusion dosage of 0.1-0.2 mEq/kg of magnesium may be given without changing hemodynamic parameters, but with higher cumulative infusion doses heart rate accelerates. Hemodynamic parameters except those related to blood pressure continued to increase to a cumulative infusion dosage of 2.0 mEq/kg. At higher cumulative infusion dosages dogs became hypotensive and the PQ interval was prolonged. However, dangerous arrhythmias were not provoked until a total dosage of 3.9 mEq/kg.  相似文献   

5.
The efficacy of milbemycin oxime was evaluated at dosages of 0.25, 0.50, and 0.75 mg/kg of body weight in dogs naturally infected with mature Ancylostoma spp, at a dosage of 0.50 mg/kg in dogs with experimentally induced immature and mature A caninum, and at dosages of 0.55 to 0.86 mg/kg in dogs naturally infected with mature Trichuris vulpis. Milbemycin oxime was 95 and 99% effective against mature Ancylostoma spp at dosages of 0.50 and 0.75 mg/kg, respectively, but only 49% effective at a dosage of 0.25 mg/kg. Efficacy was 49% against pulmonary L3-L4 stages of A caninum (36 hours after inoculation), greater than 80% against L4 (120 hours after inoculation) and early L5 stages (216 hours after inoculation), and greater than 90% against experimentally induced mature stages (360 hours after inoculation). Milbemycin oxime was also 97% effective in the removal of mature Tr vulpis from naturally infected dogs. Adverse reactions were not observed following treatment in any of the dogs.  相似文献   

6.
Serum diltiazem concentrations were evaluated following either 30 mg or 60 mg of an extended-release diltiazem administered orally once daily to 13 cats. Sequential blood samples were obtained over 24 hours. Both dosages usually resulted in elevated serum concentrations of >200 ng/mL at 6, 12, 18, and 24 hours. The 30-mg dosage was sometimes associated with low serum concentrations of <50 ng/mL at 18 and 24 hours. The 60-mg dosage (9.3 to 14.8 mg/kg) was associated with lethargy, gastrointestinal disturbances, and weight loss in nine (36%) of 25 client-owned cats. Gastrointestinal disturbances were recognized within 1 week, and weight loss was detected after 2 to 6 months of treatment.  相似文献   

7.
To determine the drug dose required to inhibit platelet reactivity by at least 50%, 2 drug regimens were evaluated in heartworm-negative, heartworm-infected, and heartworm-infected dogs embolized with dead heartworms. Aspirin, or a combination of aspirin and dipyridamole, were administered to 2 groups of Beagles (n = 5 each) for 5 to 9 days; a third group of 5 Beagles served as nontreated controls. For heartworm-negative dogs, mean (+/- SD) aspirin dosage that inhibited collagen-induced platelet reactivity by at least 50% was 6 (+/- 2) mg/kg of body weight given once daily. The aspirin/diphridamole combination dosage was 1 mg of each drug/kg given every 12 hours. All dogs (n = 15) were implanted with 7 adult heartworms each and remedicated (or not treated) beginning at 21 days after heartworm implantation. In heartworm-infected dogs, mean aspirin dosage required to inhibit collagen-induced platelet reactivity greater than or equal to 50% was 10 (+/- 6) mg/kg. Mean dosage of aspirin/dipyridamole combination was 1.6 +/- (0.5) mg of each drug/kg given every 12 hours. When platelet reactivity in response to collagen was determined to be inhibited by at least 50% in all medicated dogs, each dog (n = 15) was embolized with 7 dead adult heartworms to mimic heartworm adulticidal treatment. Platelet reactivity was monitored for 21 days after treatment, and drug dose was adjusted to maintain platelet inhibition by at least 50%. In embolized dogs, mean aspirin dosage was 17 (+/- 14) mg/kg given once daily. Mean dosage of the aspirin/dipyridamole combination was 2.8 (+/- 1.3) mg of each drug/kg given every 12 hours. All dogs (n = 15) were euthanatized 21 days after heartworm embolization. Each lung lobe was evaluated for severity of lesions and presence of organized or fibrinous thrombi. Lesion severity in the aspirin- and aspirin/dipyridamole-treated dogs was not significantly different from that in control dogs.  相似文献   

8.
OBJECTIVE: To evaluate the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl-metabolite, metabolite 1 (M1), in dogs after IV administration of a single dose and oral administration of multiple doses. ANIMALS: 7 sexually intact, female, mixed-breed dogs. PROCEDURE: A crossover study design was used so that each of the dogs received all treatments in random order. A drug-free period of 5 days was allowed between treatments. Treatments included IV administration of a single dose of PTX (15 mg/kg of body weight), oral administration of PTX with food at a dosage of 15 mg/kg (q 8 h) for 5 days, and oral administration of PTX without food at a dosage of 15 mg/kg (q 8 h) for 5 days. Blood samples were taken at 0.25, 0.5, 1, 1.5, 2, 2.5, and 3 hours after the first and last dose of PTX was administered PO, and at 5, 10, 20, 40, 80, and 160 minutes after PTX was administered IV. RESULTS: PTX was rapidly absorbed and eliminated after oral administration. Mean bioavailability after oral administration ranged from 15 to 32% among treatment groups and was not affected by the presence of food. Higher plasma PTX concentrations and apparent bioavailability were observed after oral administration of the first dose, compared with the last dose during the 5-day treatment regimens. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, oral administration of 15 mg of PTX/kg results in plasma concentrations similar to those produced by therapeutic doses in humans, and a three-times-a-day dosing regimen is the most appropriate.  相似文献   

9.
Enrofloxacin was administered orally to 6 healthy dogs at dosages of approximately 2.75, 5.5, and 11 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosage regimens. Serum and tissue cage fluid (TCF) concentrations of enrofloxacin were measured after the first and seventh treatments. The mean peak serum concentration occurred between 1 and 2.5 hours after dosing. Peak serum concentrations increased with increases in dosage. For each dosage regimen, there was an accumulation of enrofloxacin between the first and seventh treatment, as demonstrated by a significant (P = 0.001) increase in peak serum concentrations. The serum elimination half-life increased from 3.39 hours for the 2.75 mg/kg dosage to 4.94 hours for the 11 mg/kg dosage. Enrofloxacin accumulated slowly into TCF, with peak concentrations being approximately 58% of those of serum. The time of peak TCF concentrations occurred between 3.8 hours and 5.9 hours after drug administration, depending on the dosage and whether it was after single or multiple administrations. Compared with serum concentrations (area under the curve TCF/area under the curve serum), the percentage of enrofloxacin penetration into TCF was 85% at a dosage of 2.75 mg/kg, 83% at a dosage of 5.5 mg/kg, and 88% at a dosage of 11 mg/kg. All 3 dosage regimens of enrofloxacin induced continuous serum and TCF concentrations greater than the minimal concentration required to inhibit 90% (MIC90) of the aerobic and facultative anaerobic clinical isolates tested, except Pseudomonas aeruginosa.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

10.
Two hundred dogs with pituitary dependent hyperadrenocorticism (PDH) were treated with mitotane at an initial daily dosage of 21 to 69 mg/kg (mean = 45.2 mg/kg) for 5 to 14 days. During the induction period, 194 of the dogs also were given daily maintenance dosages of a glucocorticoid. Fifty of the dogs exhibited one or more adverse effects during initial induction, including weakness, vomiting, anorexia, diarrhea, and ataxia. After completion of the induction period, repeat ACTH stimulation testing revealed significant decreases in mean serum cortisol concentrations when compared with initial values. Twenty-five dogs, however, still responded to exogenous ACTH with serum cortisol concentrations above normal resting range, necessitating daily treatment for an additional 5 to 55 days. In contrast, 70 of the 200 dogs had low post-ACTH serum cortisol concentrations after the induction period. These subnormal serum cortisol concentrations generally increased spontaneously to within normal resting range 2 to 6 weeks after cessation of mitotane. In 184 dogs, mitotane was continued at an initial mean maintenance dosage of 49 mg/kg administered weekly in two to three divided doses. Of these dogs, 107 had one or more relapses of hyperadrenocorticism during treatment. In the 75 dogs that had one relapse, the median maintenance dosage was increased by approximately 35%, whereas the median maintenance dosage in the 32 dogs having two or more relapses was eventually increased by 225% over the initial dosage. After a mean maintenance treatment time of 2.0 years, the final maintenance dosage required in the 184 dogs ranged from 26.8 to 330 mg/kg/week.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

11.
Verapamil, a calcium channel-blocking drug, was administered IV at a dosage that ranged from 0.05 to 0.15 mg/kg of body weight to 14 dogs with supraventricular tachycardia. The dosage was titrated, administering 0.05 mg/kg every 5 to 30 minutes following the initial 0.05 mg/kg dose in all but 1 dog. The drug terminated the arrhythmia in 12 dogs and slowed the ventricular rate in 1 dog. One dog was unresponsive to verapamil administration and became transiently hypotensive after the administration of a total dose of 0.15 mg/kg over 5 to 6 minutes. Various arrhythmias occurred after verapamil administration, but none required additional treatment or caused serious sequelae. Verapamil was an effective treatment for acutely converting supraventricular tachycardia to sinus rhythm in these dogs. It appears to be safe when administered in the aforementioned dosage range.  相似文献   

12.
Norfloxacin, a 4-quinolone antibiotic, was administered orally to 4 healthy dogs at dosages of 11 and 22 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosing regimens. Serum and tissue cage fluid (TCF) norfloxacin concentrations were measured at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after the first and seventh dose of each dosing regimen. When administered at a dosage of 11 mg/kg, the mean peak serum concentration (Cmax) was 1.0 microgram/ml at 1 hour, the time of mean peak concentration (Tmax) after the first dose. After the seventh dose, the Cmax was 1.4 micrograms/ml at Tmax of 1.5 hours. The Tmax for the TCF concentration was 5 hours, with Cmax of 0.3 microgram/ml and 0.7 microgram/ml after the first and seventh dose, respectively. When administered at a dosage of 22 mg/kg, the serum Tmax was 2 hours after the first dose, with Cmax of 2.8 micrograms/ml. After the seventh dose, the serum Tmax was 1.5 hours, with Cmax of 2.8 micrograms/ml. The Tmax for the TCF concentration was 5 hours after the first and seventh doses, with Cmax of 1.2 micrograms/ml and 1.6 micrograms/ml, respectively. After the seventh dose, the serum elimination half-life was 6.3 hours for a dosage of 11 mg/kg and was 6.7 hours for a dosage of 22 mg/kg. For serum concentration, the area under the curve from 0 to 12 hours (AUC0----12) was 8.77 micrograms.h/ml and 18.27 micrograms.h/ml for dosages of 11 mg/kg and 22 mg/kg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

13.
Fifteen dogs were given doxorubicin, IV, at a dosage of 30 mg/m2 of body surface. A commercially available biological extract of Serratia marcescens (BESM) was administered SC to 9 of these dogs (0.04 mg/kg of body weight every third day, n = 2; 0.08 mg/kg every other day, n = 2; and 0.08 mg/kg daily, n = 5), beginning the day after administration of doxorubicin, in an attempt to find an optimal dosage and schedule of administration of BESM to reduce the duration and severity of chemotherapy-induced myelosuppression. Nine additional dogs were randomized into 3 groups of 3 dogs to receive 1 of the following dosages of BESM SC: 0.08, 0.16, and 0.32 mg/kg. Serum was harvested immediately prior to treatment and at 2, 4, 6, 8, 12, 24, 48, and 72 hours from this latter group of dogs for subsequent analysis of canine granulocyte colony-stimulating factor (G-CSF) by enzyme immunoassay. Increasing the dosage and schedule of administration of BESM reduced the duration and severity of doxorubicin-induced myelosuppression. Neutrophil counts of the group of dogs given BESM daily at a dosage of 0.08 mg/kg and the controls were evaluated statistically. The neutrophil count increased significantly (P < 0.05) above pretreatment values in BESM-treated dogs after day 7. Median neutrophil counts of the BESM-treated dogs were never significantly lower than pretreatment values, whereas the median counts of the dogs treated with doxorubicin alone were significantly below normal for 6 days (days 7-12).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

14.
The cardiovascular effects of a new nondepolarizing muscle relaxant, pancuronium bromide, were studied in mongrel dogs. Small, but significant, increases in mean arterial blood pressure were observed after each of 2 intravenous doses (0.01 mg/kg and 0.1 mg/kg) were given. Heart rate increased significantly in dogs administered the larger dosage, and indexes of ventricular functions demonstrated a trend toward positive cardiac inotrophy after either the large or the small dose.  相似文献   

15.
Concentrations of serum thyroxine (T4) and 3,5,3'-triiodothyronine (T3) were determined after the administration of freshly reconstituted thyrotropin-releasing hormone (TRH), reconstituted TRH that had been previously frozen, or thyrotropin (TSH) to 10 mature dogs (6 Greyhounds and 4 mixed-breed dogs). Thyrotropin-releasing hormone (0.1 mg/kg) or TSH (5 U/dog) was administered IV; venous blood samples were collected before and 6 hours after administration of TRH or TSH. Concentrations of the T4 and T3 were similar (P greater than 0.05) in serum after administration of freshly reconstituted or previously frozen TRH, indicating that TRH can be frozen at -20 C for at least 1 week without a loss in potency. Concentrations of T4, but not T3, were higher after the administration of TSH than they were after the administration of TRH (P less than 0.01). Concentrations of T4 increased at least 3-fold in all 10 dogs given TSH, whereas a 3-fold increase occurred in 7 of 10 dogs given freshly reconstituted or previously frozen TRH. Concentrations of T4 did not double in 1 dog given freshly reconstituted TRH and in 1 dog given previously frozen TRH. Concentrations of T3 doubled in 5 of 10, 2 of 10, and 5 of 10 dogs given TSH, freshly reconstituted TRH, or previously frozen TRH, respectively. Results suggested that concentrations of serum T4 are higher 6 hours after the administration of TSH than after administration of TRH, using dosage regimens of 5 U of TSH/dog or 0.1 mg of TRH/kg.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

16.
Serum concentrations of cefepime (BMY-28142) were determined for four dosing regimes, 10 mg/kg or 20 mg/kg, given as single subcutaneous (SC) or intramuscular injections (IM) to dogs. Serial serum samples were analyzed for the presence of cefepime by high-performance liquid chromatography. In experiment 1, the overall mean (+/- SEM) serum concentration (for a 12-hour period) after a dose of 20 mg/kg for SC and IM routes (4.9 +/- 0.74 micrograms/ml and 5.5 +/- 0.63 micrograms/ml, respectively) was twice that for the 10 mg/kg dose given either SC or IM (2.2 +/- 0.31 micrograms/ml and 2.8 +/- 0.47 micrograms/ml, respectively). There was no significant difference (p greater than 0.05) in mean serum concentrations for SC and IM routes of administration at the same dosage. In subsequent experiments, 5 doses of cefepime (20 mg/kg) were administered IM at 12-hour (experiment 2) or 24-hour (experiment 3) intervals. The mean (+/- SEM) peak serum concentration was 12.1 +/- 1.59 micrograms/ml, 2 hours after the 2nd injection in experiment 2. In experiment 3, the mean (+/- SEM) peak serum concentration was 10.9 +/- 1.34 micrograms/ml, 4 hours after the 1st injection. Mean trough concentrations in experiment 2 were greater than or equal to 0.5 microgram/ml and less than or equal to 0.5 in experiment 3. Multiple IM doses produced transient edema at the injection site and mild lameness in all dogs. Cefepime was highly active against single canine isolates of Staphylococcus intermedius, Pseudomonas aeruginosa and Escherichia coli, with minimum inhibitory concentrations of 0.125 microgram/ml, 1 microgram/ml and 0.3 microgram/ml, respectively.  相似文献   

17.
Fifteen Collies, previously having mild reactions to ivermectin challenge (120 micrograms/kg of body weight; 20 times the recommended dosage level), were studied to evaluate the effects of milbemycin oxime administration at 5 and 10 mg/kg (10 and 20 times the manufacturer's recommended dosage). Five replicates, comprising 3 dogs each, were formed on the basis of body weight. Within replicates, each dog was randomly allocated to treatment with 5 or 10 mg of milbemycin/kg or served as a untreated control. Dogs were examined repeatedly for signs of toxicosis for 4 days after treatment and daily thereafter. Two of 5 dogs treated at 5 mg/kg (10x) developed signs of mild depression on the day of treatment, but were normal 24 hours after treatment. All 5 dogs treated at 10 mg/kg (20x) developed signs of mild depression and ataxia by 6 hours. Signs persisted for 24 hours in 3 dogs. Two of these dogs also had mydriasis, whereas 3 salivated excessively. All dogs recovered completely by day 2 after treatment. The results of this study demonstrated that Collies sensitive to the effects of 120 micrograms of ivermectin (20x)/kg show similar sensitivity to the effects of milbemycin oxine administered at 10 mg/kg (20x). We conclude that ivermectin and milbemycin commercial formulations have similar margins of safety and that milbemycin toxicosis appears to be dose-dependent in Collies with a demonstrated sensitivity to ivermectin.  相似文献   

18.
Fifty-five dogs, naturally infected with Taenia sp or Dipylidium caninum or both, were assigned to the following treatment groups for dose titration studies with epsiprantel: nonmedicated control dogs (n = 14), medicated dogs given a dosage of 2.75 mg/kg of body weight (n = 15), medicated dogs given a dosage of 5.5 mg/kg (n = 16), and medicated dogs given a dosage of 8.25 mg/kg (n = 10). Medication was given orally in a tablet formulation. Feces were examined for cestodes passed and the gastrointestinal tract was examined at necropsy for retained cestodes. Efficacy of epsiprantel was 92.9% against Taenia and 44.8% against Dipylidium for a dosage of 2.75 mg/kg, 100% against Taenia and 99.8% against Dipylidium for a dosage of 5.5 mg/kg, and 94.6% against Taenia and 100% against Dipylidium for a dosage of 8.25 mg/kg. For dose confirmation, 36 dogs naturally infected with Taenia sp or D caninum or both were allotted to 2 treatment groups: nonmedicated control dogs (n = 16) and dogs medicated with epsiprantel at a dosage of 5.5 mg/kg (n = 20). Efficacy was 100% for both Taenia sp and D caninum.  相似文献   

19.
Pharmacokinetics and interactions of digoxin with phenobarbital in dogs   总被引：1，自引：0，他引：1  
In one experiment, 5 dogs were administered digoxin (0.022 mg/kg of body weight, IV), were rested for 2 weeks, were then given phenobarbital (13.2 mg/kg orally) for 14 days, and then were given digoxin again (0.022 mg/kg, IV). Comparing prephenobarbital (control) digoxin half-lives of 42.4 +/- 8.8 hours and postphenobarbital digoxin half-lives of 18.0 +/- 2.2 hours, the half-life was significantly (P less than 0.05) decreased after phenobarbital administration. Clearance was increased by 84%, and the volume of distribution given was decreased by 34%. In a second experiment, 5 dogs were given digoxin (0.022 mg/kg, orally) daily for 11 days, and the digoxin kinetics were evaluated after the last dosing. The dogs were then rested and given phenobarbital (13.2 mg/kg, orally) once daily for 14 days and digoxin (0.022 mg/kg) once daily for 11 days, and the pharmacokinetics of digoxin was determined on the last day of dosing. Significant differences in steady-state serum concentrations and the pharmacokinetics of digoxin were not found between the control and phenobarbital phases of the experiment. Mean (+/- SD) half-lives of digoxin were 29.0 +/- 7.2 hours before phenobarbital treatment (control) and were 34.8 +/- 7.2 hours after phenobarbital treatment. In comparing results of the single-dose experiment vs the oral multiple-dose experiment, dogs had shorter half-lives for digoxin after multiple dosing. Therefore, if phenobarbital and digoxin are to be chronically coadministered orally, an adjustment in the digoxin dose is not necessary.  相似文献   

20.
Isoxsuprine (0.6 mg/kg) administered IV to 6 standing horses produced substantial, transient decreases in systemic blood pressure, systemic vascular resistance, and stroke volume. It also produced substantial, transient increases in heart rate, cardiac output, and purposeful movement. Plasma concentrations of isoxsuprine peaked soon after the drug was administered IV and then decreased over a 12-hour period in a biexponential manner, with distribution and elimination half-lives of 14 minutes and 2.67 hours, respectively. Total body clearance and steady-state volume of distribution were calculated to be 53.8 ml/min/kg and 10.5 L/kg, respectively. When a recommended therapeutic dosage regimen (0.6 mg/kg 2 times a day, per os) was used in 4 of these horses, changes were not detected. Isoxsuprine was not detected in plasma after the drug was given orally. We conclude that 0.6 mg of isoxsuprine/kg given orally every 12 hours is not likely to produce cardiovascular changes in the resting horse and that this is probably because plasma concentrations are not high enough to do so.  相似文献   

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