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1.
To evaluate the effects of compensated heart failure (HF) on digoxin pharmacokinetic properties in cats, 6 cats with dilated cardiomyopathy were compared with 6 clinically normal (control) cats. Digoxin tablets were administered at a dosage of 0.01 mg/kg of body weight, q 48 h for approximately 10 days, until presumed steady state was reached. Both groups were treated concomitantly with aspirin, furosemide, and a commercial low-salt diet. Retrospectively, control and HF cats were calculated to be at 95% and 97% steady state, respectively. At the time blood samples were collected, HF cats were clinically compensated. Serum digoxin concentration [( DXN]) was determined by radioimmunoassay on samples drawn immediately before and 1, 2, 4, 8, 12, 24, 34, and 48 hours after digoxin administration. Measured and calculated values (peak, 8-hour, and mean [DXN]; elimination half-life [t1/2]; oral clearance; and hours during which [DXN] was in the toxic range) were not significantly different between control and HF cats. To predict individual propensity for digoxin intoxication, serum creatinine and urea concentrations and sulfobromophthalein dye retention were measured in control and HF cats prior to the onset of treatment with digoxin. There was no statistically significant correlation between serum creatinine and urea concentrations when compared with sulfobromophthalein dye retention nor between any of these values and digoxin peak, 8-hour, and mean concentrations or t1/2, oral clearance, or hours during which [DXN] was in the toxic range. Mean serum creatinine and urea nitrogen concentrations were significantly greater (P less than 0.01) and sulfobromophthalein dye retention approached significant prolongation (P less than 0.06) in HF cats, compared with that in control cats.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

2.
OBJECTIVE: To compare pharmacokinetic and pharmacodynamic characteristics of fentanyl citrate after IV or transdermal administration in cats. ANIMALS: 6 healthy adult cats with a mean weight of 3.78 kg. PROCEDURE: Each cat was given fentanyl IV (25 mg/cat; mean +/- SD dosage, 7.19 +/- 1.17 mg/kg of body weight) and via a transdermal patch (25 microg of fentanyl/h). Plasma concentrations of fentanyl were measured by use of radioimmunoassay. Pharmacokinetic analyses of plasma drug concentrations were conducted, using an automated curve-stripping process followed by nonlinear, least-squares regression. Transdermal delivery of drug was calculated by use of IV pharmacokinetic data. RESULTS: Plasma concentrations of fentanyl given IV decreased rapidly (mean elimination half-life, 2.35 +/- 0.57 hours). Mean +/- SEM calculated rate of transdermal delivery of fentanyl was 8.48 +/- 1.7 mg/h (< 36% of the theoretical 25 mg/h). Median steady-state concentration of fentanyl 12 to 100 hours after application of the transdermal patch was 1.58 ng/ml. Plasma concentrations of fentanyl < 1.0 ng/ml were detected in 4 of 6 cats 12 hours after patch application, 5 of 6 cats 18 and 24 hours after application, and 6 of 6 cats 36 hours after application. CONCLUSIONS AND CLINICAL RELEVANCE: In cats, transdermal administration provides sustained plasma concentrations of fentanyl citrate throughout a 5-day period. Variation of plasma drug concentrations with transdermal absorption for each cat was pronounced. Transdermal administration of fentanyl has potential for use in cats for long-term control of pain after surgery or chronic pain associated with cancer.  相似文献   

3.
Healthy mature roosters (n = 10) were given gentamicin (5 mg/kg of body weight, IV) and, 30 days later, another dose IM. Serum concentrations of gentamicin were determined over 60 hours after each drug dosing, using a radioimmunoassay. Using nonlinear least-square regression methods, the combined data of IV and IM treatments were best fitted by a 2-compartment open model. The mean distribution phase half-life was 0.203 +/- 0.075 hours (mean +/- SD) and the terminal half-life was 3.38 +/- 0.62 hours. The volume of the central compartment was 0.0993 +/- 0.0097 L/kg, volume of distribution at steady state was 0.209 +/- 0.013 L/kg, and the total body clearance was 46.5 +/- 7.9 ml/h/kg. Intramuscular absorption was rapid, with a half-life for absorption of 0.281 +/- 0.081 hours. The extent of IM absorption was 95 +/- 18%. Maximal serum concentration of 20.68 +/- 2.10 micrograms/ml was detected at 0.62 +/- 0.18 hours after the dose. Kinetic calculations predicted that IM injection of gentamicin at a dosage of 4 mg/kg, q 12 h, and 1.5 mg/kg, q 8 h, would provide average steady-state serum concentrations of 6.82 and 3.83 micrograms/ml, with minimal steady-state serum concentrations of 1.54 and 1.50 micrograms/ml and maximal steady-state serum concentrations of 18.34 and 7.70 micrograms/ml, respectively.  相似文献   

4.
Pharmacokinetic variables were calculated from time-concentration data obtained after IV (10 mg/kg of body weight; n =9) and oral (12.5 mg/kg to group A [n = 3]; 25 mg/kg to group B [n = 3]; and 50 mg/kg to group C [n = 3] pigs) cyclosporine (formerly, cyclosporine A) administration. Resulting mean (+/- SD) pharmacokinetic variables were as follows: half life of distribution, 0.96 (+/- 0.7) hours; half life of elimination, 7.71 (+/- 2.6) hours; volume of distribution at steady state, 4.47 (+/- 2.22) L/kg; volume of the central compartment, 1.71 (+/- 0.78) L/kg; and systemic clearance, 8.95 (+/- 2.7) ml/kg/min. Oral bioavailability was: overall 57 (+/- 19) %; group A, 44 (+/- 11) %; group B, 78 (+/- 15) %; group C, 48 (+/- 6) %. Time to peak concentration was 3.55 (+/- 0.88) hours. During the 22 days of daily oral cyclosporine administration, blood 24-hour trough concentrations were: group A, 224.3 (+/- 78.4) ng/ml; group B, 640.7 (+/- 174.6) ng/ml; and group C, 2,344 (+/- 1,095) ng/ml. Lymphoblast transformation stimulation index was suppressed in all pigs except 1, which had a corresponding cyclosporine concentration of 92.4 ng/ml. Minimal, although statistically significant, decreases in serum albumin and magnesium concentrations and increases in serum creatinine and urea nitrogen concentrations were evident in pigs of some treatment groups. Histologic examination of necropsy specimens revealed mild hepatic necrosis (n = 1 pig), renal tubular dilatation (n = 5), and pulmonary inflammation (n = 2). Pigs given 25 and 50 mg of cyclosporine/kg failed to gain weight.  相似文献   

5.
OBJECTIVE: To determine pharmacokinetics of single and multiple doses of rimantadine hydrochloride in horses and to evaluate prophylactic efficacy of rimantadine in influenza virus-infected horses. ANIMALS: 5 clinically normal horses and 8 horses seronegative to influenza A. PROCEDURE: Horses were given rimantadine (7 mg/kg of body weight, i.v., once; 15 mg/kg, p.o., once; 30 mg/kg, p.o., once; and 30 mg/kg, p.o., q 12 h for 4 days) to determine disposition kinetics. Efficacy in induced infections was determined in horses seronegative to influenza virus A2. Rimantadine was administered (30 mg/kg, p.o., q 12 h for 7 days) beginning 12 hours before challenge-exposure to the virus. RESULTS: Estimated mean peak plasma concentration of rimantadine after i.v. administration was 2.0 micrograms/ml, volume of distribution (mean +/- SD) at steady-state (Vdss) was 7.1 +/- 1.7 L/kg, plasma clearance after i.v. administration was 51 +/- 7 ml/min/kg, and beta-phase half-life was 2.0 +/- 0.4 hours. Oral administration of 15 mg of rimantadine/kg yielded peak plasma concentrations of < 50 ng/ml after 3 hours; a single oral administration of 30 mg/kg yielded mean peak plasma concentrations of 500 ng/ml with mean bioavailability (F) of 25%, beta-phase half-life of 2.2 +/- 0.3 hours, and clearance of 340 +/- 255 ml/min/kg. Multiple doses of rimantadine provided steady-state concentrations in plasma with peak and trough concentrations (mean +/- SEM) of 811 +/- 97 and 161 +/- 12 ng/ml, respectively. Rimantadine used prophylactically for induced influenza virus A2 infection was associated with significant decreases in rectal temperature and lung sounds. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of rimantadine to horses can safely ameliorate clinical signs of influenza virus infection.  相似文献   

6.
The role of digoxin in treatment of cats with dilated cardiomyopathy and other forms of myocardial failure is unclear. We evaluated the chronotropic and inotropic effects of digoxin by comparing baseline, noninvasive indices of cardiac performance with those obtained after 9 +/- 1.3 (mean +/- SEM) days of digoxin treatment in 6 cats with heart failure attributable to dilated cardiomyopathy. Two-dimensionally directed, M-mode echocardiography and electrocardiography were used to determine left ventricular shortening fraction, preejection period (PEP), ejection time (LVET), PEP to LVET ratio, velocity of circumferential fiber shortening, electromechanical systole, heart rate, and PR interval. Treatment consisted of administration of furosemide (mean dosage, 2.4 mg/kg of body weight/day), digoxin in tablet form (approximately 0.01 mg/kg, q 48 h), aspirin (80 mg, q 48 h), and a commercial low-salt diet. In addition, 2 cats were administered short-term, low-dose fluids IV, and 2 were given taurine supplementation at rates of 500 and 1,000 mg/day. Other off-loading or inotropic agents were not administered. Therapeutic or toxic serum digoxin concentration was achieved in all cats. Significant (P less than 0.05) improvement was detected in mean values for shortening fraction, PEP, PEP to LVET ratio, and velocity of circumferential fiber shortening. Mean electromechanical systole and LVET did not change significantly. Improvement, as assessed by indices of cardiac function, was documented in 4 of the 6 cats treated with digoxin, including the 2 cats given taurine supplementation. In the cats given taurine, positive inotropic effect was observed prior to the time when taurine-induced improvement in ventricular function is detectable.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

7.
Mature boars were subjected to chronic treatment with a gonadotropin-releasing hormone (GnRH) agonist, goserelin (D-Ser[But]6, Azgly-NH210), and serum luteinizing hormone (LH) and testosterone concentrations were measured. Ten sexually mature boars were randomly assigned to treatment (n = 5) or control (n = 5) groups. On day 0, boars were implanted sc (day 0) with 2 GnRH agonist implants (1 mg of GnRH/implant) or sham implants. Blood samples were collected at 12-hour intervals on days -2 and -1, at 6-hour intervals on days 0 through 4, and at 12-hour intervals on days 5 through 8. In addition, blood samples were collected at 15-minute intervals for 6 hours on days -1, 0, 4, and 8. Serum testosterone and LH concentrations were determined by radioimmunoassay. Maximal LH (7 +/- 1 ng/ml) and testosterone (26 +/- 3 ng/ml) concentrations were observed at 5 and 18 hours, respectively, after GnRH agonist treatment. Subsequently, LH and testosterone concentrations decreased to pretreatment values (0.3 +/- 0.1 ng/ml and 1.8 +/- 0.4 ng/ml, respectively) by 24 and 48 hours, respectively, after GnRH agonist implantation. Few differences in the characteristics of pulsatile LH release were observed between the groups. Testosterone and LH concentrations in samples collected at 6- and 12-hour intervals and pulsatile LH release did not change after sham treatment of control boars. Whereas previous reports indicated that chronic GnRH administration suppressed serum LH and testosterone concentrations in rams, rats, and dogs, our results indicate that chronic GnRH agonist treatment induced transitory increases, without subsequent suppression, in LH and testosterone concentrations in mature boars.  相似文献   

8.
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   

9.
The pharmacokinetics of selamectin were evaluated in cats and dogs, following intravenous (0.05, 0.1 and 0.2 mg/kg), topical (24 mg/kg) and oral (24 mg/kg) administration. Following selamectin administration, serial blood samples were collected and plasma concentrations were determined by high performance liquid chromatography (HPLC). After intravenous administration of selamectin to cats and dogs, the mean maximum plasma concentrations and area under the concentration-time curve (AUC) were linearly related to the dose, and mean systemic clearance (Clb) and steady-state volume of distribution (Vd(ss)) were independent of dose. Plasma concentrations after intravenous administration declined polyexponentially in cats and biphasically in dogs, with mean terminal phase half-lives (t(1/2)) of approximately 69 h in cats and 14 h in dogs. In cats, overall Clb was 0.470 +/- 0.039 mL/min/kg (+/-SD) and overall Vd(ss) was 2.19 +/- 0.05 L/kg, compared with values of 1.18 +/- 0.31 mL/min/kg and 1.24 +/- 0.26 L/kg, respectively, in dogs. After topical administration, the mean C(max) in cats was 5513 +/- 2173 ng/mL reached at a time (T(max)) of 15 +/- 12 h postadministration; in dogs, C(max) was 86.5 +/- 34.0 ng/mL at T(max) of 72 +/- 48 h. Bioavailability was 74% in cats and 4.4% in dogs. Following oral administration to cats, mean C(max) was 11,929 +/- 5922 ng/mL at T(max) of 7 +/- 6 h and bioavailability was 109%. In dogs, mean C(max) was 7630 +/- 3140 ng/mL at T(max) of 8 +/- 5 h and bioavailability was 62%. There were no selamectin-related adverse effects and no sex differences in pharmacokinetic parameters. Linearity was established in cats and dogs for plasma concentrations up to 874 and 636 ng/mL, respectively. Pharmacokinetic evaluations for selamectin following intravenous administration indicated a slower elimination from the central compartment in cats than in dogs. This was reflected in slower clearance and longer t(1/2) in cats, probably as a result of species-related differences in metabolism and excretion. Inter-species differences in pharmacokinetic profiles were also observed following topical administration where differences in transdermal flux rates may have contributed to the overall differences in systemic bioavailability.  相似文献   

10.
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   

11.
Ten horses, a pony, and 13 cats were used to evaluate base-line blood ammonia, bilirubin, and urea nitrogen concentrations and to determine The effects of prolonged cold storage (-20 degrees C) before assay. Base-line plasma ammonia concentrations in cats (0.992 +/- 0.083 [SE] micrograms/ml) did not change significantly after 48 hours of storage (0.871 +/- 0.073 micrograms/ml); however, they were increased 4.2- and 13-fold after 168 and 216 hours of storage, respectively. In contrast to base-line plasma-ammonia values in cats, those of horses were significantly (0.265 +/- 0.044 micrograms/ml) lower, and significantly increased from base-line values after 48 hours of storage (0.861 +/- 0.094 micrograms/ml) and continued to increase 25.6-fold at 168 hours and 18.4-fold at 216 hours. Plasma urea nitrogen concentrations in cats (25.8 +/- 1.06 mg/dl) and horses (11.2 +/- 0.749 mg/dl) did not change significantly during 168 hours of storage. Total plasma bilirubin values from both cats (0.19 +/- 0.049 mg/dl) and horses (0.75 +/- 0.064 mg/dl) also did not change significantly during storage. These results indicate that feline plasma samples for ammonia determinations may be stored at -20 degrees C for up to 48 hours, whereas equine plasma ammonia values tend to increase during that time. The reason for the increase remains unexplained. Both feline and equine plasma urea nitrogen and total bilirubin are stable for at least 168 hours of storage at -20 degrees C.  相似文献   

12.
Digoxin was administered orally and intravenously to seven healthy adult mares and geldings in two separate trials. At a dose of 44 microgram digoxin/kg body weight, the oral study was characterized by an absorption phase with a mean (+/- 1 standard deviation) peak serum digoxin concentration of 2.21 ng/ml (+/- 0.45) at a mean of 2.29 h (+/- 1.52) after administration. A second rise in serum digoxin concentration started about 6-8 h after administration and extended to about 20 h after administration. The mean bioavailability (F) was 23.38% (+/- 5.96). At a dose of 22 microgram digoxin/kg body weight, the intravenous study was characterized by a two-compartment model with the following mean pharmacokinetic measurements: distribution rate constant (alpha), 1.391 h-1 (+/- 0.1909); zero-time serum digoxin concentration determined from the distribution phase (A), 21.247 ng/ml (+/- 5.6614); elimination rate constant (beta), 0.0409 h-1 (+/- 0.0069); zero-time serum digoxin concentration determined from the elimination phase (B), 3.82 ng/ml (+/- 0.433); apparent specific volume of distribution uncorrected for protein binding (Vd beta), 5.003 l/kg (+/- 0.5177). The mean beta corresponded to a biological half-life (T1/2 beta) of 16.9 h. Based upon results of this study, theoretically achievable steady-state serum digoxin concentrations were calculated for maintenance doses given by oral and intravenous routes of administration with appropriate two-compartment, multiple-dose formulae. Loading doses were also calculated for each route. It is the opinion of the authors that the oral route of administration of digoxin is effective in the horse and may preclude the potential risks posed by the high serum digoxin concentrations immediately following intravenous administration.  相似文献   

13.
Six mature Holstein bulls were given an 8-day course of phenylbutazone (PBZ) orally (loading dose, 12 mg of PBZ/kg of body weight and 7 maintenance doses of 6 mg of PBZ/kg, q 24 h). Plasma concentration-vs-time data were analyzed, using nonlinear regression modeling. The harmonic mean +/- pseudo-SD of the biologic half-life of PBZ was 61.8 +/- 12.8 hours. The arithmetic mean +/- SEM of the total body clearance and apparent volume of distribution were 0.0021 +/- 0.0001 L/h/kg and 0.201 +/- 0.009 L/kg, respectively. The predicted mean minimal plasma concentration of PBZ with this dosage regimen was 75.06 +/- 4.05 micrograms/ml. The predicted minimal plasma drug concentration was compared with the observed minimal plasma drug concentration in another group of bulls treated with PBZ for at least 60 days. Sixteen mature Holstein bulls were given approximately 6 mg of PBZ/kg, PO, daily for various musculoskeletal disorders. The mean observed minimal plasma concentration of PBZ in the 16 bulls was 76.10 +/- 2.04 micrograms/ml, whereas the mean predicted minimal plasma concentration was 74.69 +/- 3.10 micrograms/ml. Dosages of 4 to 6 mg of PBZ/kg, q 24 h, or 10 to 14 mg of PBZ/kg, q 48 h, provided therapeutic plasma concentrations of PBZ with minimal steady-state concentrations between 50 and 70 micrograms/ml.  相似文献   

14.
Progesterone was administered IM to 6 adult anestrous bitches at a dosage of 2 mg/kg of body weight. Serum progesterone concentrations were measured prior to progesterone administration and for 72 hours thereafter. The serum progesterone concentration time data were analyzed by use of a pharmacokinetics modeling computer program. The mean (+/- SD) peak serum progesterone concentration (34.3 +/- 7.8 ng/ml) was reached at 1.8 +/- 0.2 hours after progesterone administration. The mean serum progesterone concentration was 6.9 +/- 1.4 ng/ml at 24 hours and 2.0 +/- 0.4 ng/ml at 48 hours after progesterone administration. By 72 hours after administration, mean serum progesterone concentration was 0.9 +/- 0.2 ng/ml, which was comparable to serum progesterone concentrations prior to injection. The mean half-life of the absorption phase was 0.5 hours (range, 0.3 to 0.7 hours). The mean half-life of elimination was 12.1 hours (range, 9.5 to 13.8 hours). By analysis of the data, it was established that a dosage of 3 mg/kg, when the hormone was given IM to dogs once a day, would maintain serum progesterone concentration greater than 10 ng/ml.  相似文献   

15.
OBJECTIVE: To determine the pharmacokinetics of gallium maltolate (GaM) after intragastric administration in healthy foals. ANIMALS: 6 healthy neonatal foals. PROCEDURES: Each foal received GaM (20 mg/kg) by intragastric administration. Blood samples were obtained before (time 0) and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, and 48 hours after GaM administration for determination of serum gallium concentrations by use of inductively coupled plasma mass spectroscopy. RESULTS: Mean +/- SD pharmacokinetic variables were as follows: peak serum gallium concentration, 1,079 +/- 311 ng/mL; time to peak serum concentration, 4.3 +/- 2.0 hours; area under the serum concentration versus time curve, 40,215 +/- 8,420 ng/mL/h; mean residence time, 39.5 +/- 17.2 hours; area under the moment curve, 1,636,554 +/- 931,458 ng([h](2)/mL); and terminal half-life, 26.6 +/- 11.6 hours. The mean serum concentration of gallium at 12 hours was 756 +/- 195 ng/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Gallium maltolate administered via nasogastric tube at a dose of 20 mg/kg to neonatal foals resulted in gallium serum concentrations considered sufficient to suppress growth or kill Rhodococcus equi in macrophages and other infected tissues.  相似文献   

16.
OBJECTIVE: To establish a dosing regimen for potassium bromide and evaluate use of bromide to treat spontaneous seizures in cats. DESIGN: Prospective and retrospective studies. ANIMALS: 7 healthy adult male cats and records of 17 cats with seizures. PROCEDURE: Seven healthy cats were administered potassium bromide (15 mg/kg [6.8 mg/lb], p.o., q 12 h) until steady-state concentrations were reached. Serum samples for pharmacokinetic analysis were obtained weekly until bromide concentrations were not detectable. Clinical data were obtained from records of 17 treated cats. RESULTS: In the prospective study, maximum serum bromide concentration was 1.1 +/- 0.2 mg/mL at 8 weeks. Mean disappearance half-life was 1.6 +/- 0.2 weeks. Steady state was achieved at a mean of 5.3 +/-1.1 weeks. No adverse effects were detected and bromide was well tolerated. In the retrospective study, administration of bromide (n = 4) or bromide and phenobarbital (3) was associated with eradication of seizures in 7 of 15 cats (serum bromide concentration range, 1.0 to 1.6 mg/mL); however, bromide administration was associated with adverse effects in 8 of 16 cats. Coughing developed in 6 of these cats, leading to euthanasia in 1 cat and discontinuation of bromide administration in 2 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Therapeutic concentrations of bromide are attained within 2 weeks in cats that receive 30 mg/kg/d (13.6 mg/lb/d) orally. Although somewhat effective in seizure control, the incidence of adverse effects may not warrant routine use of bromide for control of seizures in cats.  相似文献   

17.
Plasma cortisol (hydrocortisone) was measured by radioimmunoassay in 6 normal cats. Blood was collected from the cats by venipuncture at intervals of 3 hours for 3 days. Resting plasma cortisol concentrations averaged 17.0 +/- 2.8 (SD) ng/ml and ranged from nondetectable (less than 3 ng/ml) to 82.8 ng/ml. Of 144 plasma samples, 95% contained less than 40 ng of cortisol/ml. Circadian rhythm of cortisol secretion was not detected, suggesting that adrenal function tests may be started in feline patients at any time of day. Intramuscular injection of 2.2 U of ACTH gel/kg of body weight caused detectable increase in plasma cortisol concentrations at 1 and 2 hours after injection. Maximal response to ACTH in the 6 cats ranged from 41.6 to 178.4 ng/ml. Oral administration of 0.1 mg of dexamethasone/kg suppressed plasma cortisol to nondetectable concentrations for 32 hours in 5 of the 6 cats.  相似文献   

18.
Pharmacokinetics of amikacin in cats   总被引：1，自引：0，他引：1  
Six mixed-breed adult cats were given 5 mg of amikacin sulfate/kg of body weight by rapid IV, IM, and SC routes of administration. The serum concentration-vs-time data were analyzed, using a noncompartmental model. The harmonic mean +/- pseudo-SD of the effective half-life of amikacin was 78.8 +/- 19.3 minutes after IV administration, 118.7 +/- 14.4 minutes after IM administration, and 117.7 +/- 12.8 minutes after SC administration. The arithmetic mean +/- SD of mean residence time was 118.3 +/- 21.7 minutes, 173.4 +/- 19.9 minutes, and 171.7 +/- 19.1 minutes after IV, IM, and SC drug administration, respectively. The mean apparent volume of distribution at steady state was 0.17 +/- 0.02 L/kg, and the mean total body clearance was 1.46 +/- 0.26 ml/min/kg. Mean bioavailability was 95 +/- 20% after IM administration and 123 +/- 33% after SC drug administration. A recommended dosage of 10 mg/kg, q 8 h can be expected to provide a therapeutic serum concentration of amikacin with a mean steady-state concentration of 14 micrograms/ml. The SC route of administration is preferred, because of rapid absorption, good bioavailability, and ease of administration.  相似文献   

19.
The pharmacokinetic properties of marbofoxacin, a third generation fluoroquinolone, were investigated in 12 healthy adult cats after single subcutaneous (SC) administration of 2 mg/kg BW (Part I, n=8 cats) and 4 mg/kg BW (Part II, n=4 cats). In each part of the study blood and urine samples were collected before treatment and thereafter for 5 days. The plasma and urine concentrations of marbofloxacin were determined by HPLC with UV detection. Pharmacokinetic calculations were performed for each treated animal using an open one-compartment-model with first-order elimination after SC dosing. Marbofloxacin in plasma (means): Maximum concentrations (Cmax) of about 1.2 and 3.0 microg/ml were measured 2.3 and 4 hours (tmax) after dosing of 2 and 4 mg/kg BW, respectively. Elimination from the body was low with a total clearance (Cl/F) of approximately 0.1 l/h/kg for both dosages. The half-life (t 1/2) for this process was calculated with 8-10 hours. AUC increased almost proportional when doubling the dose, i.e., 19.77 +/- 6.25 microg * h/ml (2 mg/kg BW) and 51.26 +/- 11.83 microg * h/ml (4 mg/kg BW). Plasma kinetics measured were in accordance with data from literature. Marbofloxacin in urine (means): Maximum drug concentrations were detected 4 and 8 hours after dosing with 70 microg/ml (2 mg/kg BW) and 160 microg/ml (4 mg/kg BW), respectively. Inhibitory effects of the urinary matrix on the antimicrobial activity of the drug were taken into account when performing PK/PD calculations. However, a concentration-dependent bactericidal activity (Cmax/MIC > 8-10) which is claimed for fluoroquinolones was sufficiently met with focus on Escherichia (E.) coli (MIC90 0.5 microg/ml). In the same matrix a threshold value of 1.0 microg/ml was undercut 82 and 116 hours after SC dosing, respectively. Hence, a time-dependent bacteria killing kinetic (T > MIC) which may be of relevance for some Gram-positive germs like Staphylococcus spp. (MIC90 1.0 microg/ml) should be covered, too.  相似文献   

20.
OBJECTIVE: To describe pharmacokinetics of multi-dose oral administration of tacrolimus in healthy cats and evaluate the efficacy of tacrolimus in the prevention of allograft rejection in cats with renal transplants. ANIMALS: 6 healthy research cats. PROCEDURE: Cats received tacrolimus (0.375 mg/kg, PO, q 12 h) for 14 days. Blood tacrolimus concentrations were measured by a high performance liquid chromatography-mass spectrometry assay. Each cat received an immunogenically mismatched renal allograft and native kidney nephrectomy. Tacrolimus dosage was modified to maintain a target blood concentration of 5 to 10 ng/mL. Cats were euthanatized if plasma creatinine concentration exceeded 7 mg/dL, body weight loss exceeded 20%, or on day 50 after surgery. Kaplan-Meier survival curves were plotted for 6 cats treated with tacrolimus and for 8 cats with renal transplants that did not receive immunosuppressive treatment. RESULTS: Mean (+/- SD) values of elimination half-life, time to maximum concentration, maximum blood concentration, and area under the concentration versus time curve from the last dose of tacrolimus to 12 hours later were 20.5 +/- 9.8 hours, 0.77 +/- 0.37 hours, 27.5 +/- 31.8 ng/mL, and 161 +/- 168 hours x ng/mL, respectively. Tacrolimus treated cats survived longer (median, 44 days; range, 24 to 52 days) than untreated cats (median, 23 days; range, 8 to 34 days). On histologic evaluation, 3 cats had evidence of acute-active rejection, 1 cat had necrotizing vasculitis, and 2 cats euthanatized at study termination had normal appearing allografts. CONCLUSIONS AND CLINICAL RELEVANCE: Tacrolimus may be an effective immunosuppressive agent for renal transplantation in cats.  相似文献   

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