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1.
The pharmacokinetics of enalapril (0.5 mg/kg i.v.) and the pharmacodynamics of enalapril (0.5 mg/kg PO) in 5 mares were investigated. After single i.v. dosing, concentrations of enalapril and enalaprilat, its active metabolite, were measured. Two weeks later, enalapril was administered by nasogastric tube. Potassium, creatinine, blood urea nitrogen (BUN), enalapril, and enalaprilat concentrations and angiotensin converting enzyme (ACE) activity were measured in serum. In addition, heart rate, blood pressure, digital venous blood gases, and lactate were measured. Two weeks later, enalapril was again administered by nasogastric tube. To mimic activation of the renin-angiotensin-aldosterone system, angiotensin I (0.5 microg/kg) was administered at fixed intervals, followed by blood-pressure and heart-rate measurement. The elimination half lives of enalapril and enalaprilat were 0.59 and 1.25 hours, respectively, after i.v. administration. After PO administration, enalapril and enalaprilat were not detectable in serum. There was a tendency (P = .0625) toward a decrease in ACE activity 45-120 minutes after enalapril administration, but ACE activity suppression was never > 16%. There was a tendency (P = .0625) toward a decrease in mean arterial pressure (MAP) 6-8 hours after enalapril administration. Serum concentrations of potassium, creatinine, and BUN and digital venous blood gases and lactate concentrations did not change. In response to angiotensin I, there was a tendency (P = .0625) toward a decrease in the MAP response 4-24 hours after enalapril administration. Single-dose enalapril at 0.5 mg/kg PO did not demonstrate significant availability, pharmacodynamic effect, or substantial suppression of ACE activity.  相似文献   

2.
OBJECTIVE: To evaluate blood pressure, renal function, and the renin-angiotensin-aldosterone system (RAAS) in cats with autosomal dominant polycystic kidney disease (ADPKD) and to assess the effect of enalapril on these variables. ANIMALS: 6 cats with ADPKD and 6 age-matched healthy cats. PROCEDURE: To measure blood pressure and heart rate, a radiotelemetry catheter was placed in the left femoral artery of each cat. Baseline data collection included 24-hour blood pressure, heart rate, and motor activity. Blood was then collected for analysis of RAAS status and renal function. Enalapril (0.5 mg/kg of body weight, p.o., q 24 h) was administered for 1 week, and data collection was repeated. RESULTS: Differences in baseline blood pressure, heart rate, motor activity, RAAS status, and renal function were not detected between cats with ADPKD and control cats. Hypertension was not documented in cats with ADPKD. Blood pressure was significantly reduced for 15 to 17 hours after treatment with enalapril in both groups. Administration of enalapril also resulted in significant increases in plasma renin activity and significant decreases in angiotensin converting enzyme activity and atrial natriuretic peptide concentration but only minimal changes in glomerular filtration rate and effective renal plasma flow in both groups of cats. CONCLUSIONS AND CLINICAL RELEVANCE: Although hypertension is common in humans with ADPKD, cats with ADPKD were normotensive. Treatment with enalapril (0.5 mg/kg, p.o., q 24 h) significantly reduced blood pressure in normotensive healthy cats and cats with ADPKD, and resulted in predictable changes in RAAS enzyme activities and hormone concentrations. Enalapril had minimal effects on renal function.  相似文献   

3.
The plasma pharmacokinetics of benazepril and its active metabolite, benazeprilat, were determined in cats after oral administration of benazepril.HCl at dosages of 0.25, 0.5 and 1.0 mg/kg as a single dose (n = 5 per group) and after once daily application for 8 days (n = 6 per group). Pharmacodynamics were assessed by measurement of plasma angiotensin converting enzyme (ACE) activity. After single administration of benazepril.HCl, maximum benazepril concentrations were recorded at the first sample (2 h) and declined relatively rapidly with an elimination half life (t1/2) of 1.4 h. Highest benazeprilat concentrations were recorded at the first sample (2 h) in most cats and declined biphasically with half lives of each phase of 2.4 and 27.7 h. With repeated administration, plasma benazeprilat concentrations accumulated slightly with accumulation ratios (R) of 1.46, 1.36 and 1.24 for the 0.25, 0.5 and 1.0 mg/kg dosages of benazepril.HCl, respectively (median value of 1.36 for all dosages). All three dosages of benazepril.HCl caused marked inhibition of plasma ACE activity in all cats. The maximum effect (Emax, % inhibition of ACE as compared to baseline) was > or = 98% after single and 100% with repeated administration. The duration of action of benazepril.HCl was long, with > 87% (single) and > 90% (repeat) inhibition of plasma ACE persisting 24 h after dosing. Benazepril.HCl was well tolerated in all animals. Dosages of 0.25-1.0 mg/kg benazepril.HCl once daily are recommended for clinical testing in cats.  相似文献   

4.
To support their combined use, the objective of the study was to evaluate the effects of benazepril and pimobendan on serum angiotensin‐converting enzyme (ACE) activity in dogs. A total of 48 healthy beagle dogs were randomized into four groups (n = 12 per group) in a parallel‐group design study: A (control, placebo twice daily (BID)); B (0.5–1.0 mg/kg benazepril once daily (SID) in the morning, placebo in the evening); C (0.25–0.5 mg/kg benazepril BID); D (0.25–0.5 mg/kg benazepril and 0.125–0.25 mg/kg pimobendan, both BID). The test items were administered orally for 15 days. Serum ACE activity was measured on days 1 and 15. Groups B, C and D had significantly lower average serum ACE activity compared to baseline and to the control group, on both days 1 and 15. There were no significant differences in average ACE activity between groups B, C and D. Noninferiority of group C to B was demonstrated. In conclusion, 0.25–0.5 mg/kg benazepril administered BID produced noninferior inhibition of serum ACE activity compared to 0.5–1.0 mg/kg benazepril dosed SID. Pimobendan had no significant effect on benazepril's action on serum ACE activity. The results support the use of benazepril BID in dogs and in combination with pimobendan.  相似文献   

5.
In order to evaluate the effect of enalapril on haemodynamics and renal function in a pressure overload model, we prepared eight feline models of left ventricular hypertrophy (LVH) by banding of the aortic arch. The LVH cats were assigned to the placebo group or the enalapril group (0.5 mg/kg, PO, sid) 3 months following surgery, and each received its respective drug for 4 weeks. Each week, blood pressure, angiotensin converting enzyme (ACE) activity in blood, and creatinine clearance were measured, and complete blood count (CBC), biochemical examination of the blood, echocardiography, and chest radiography were carried out. The interventricular septum thickness (IVSd, IVSs), fractional shortening (FS), and ejection fraction (EF) increased significantly in the LVH cats following surgery (P<0.05). There was no significant difference between the placebo group and the enalapril group with respect to general physical parameters, CBC, biochemical parameters and renal function. In the enalapril group, systolic arterial pressure, mean arterial pressure, and ACE activity in blood decreased significantly following administration (P<0.05). In addition, the left ventricular free wall thickness in diastole and IVSd decreased significantly following administration (P<0.05). These results suggest that, in a pressure overload model, enalapril (0.5 mg/kg, sid) inhibits cardiac hypertrophy, reduces blood pressure, and does not adversely affect renal function.  相似文献   

6.
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   

7.
Excessive aldosterone secretion is detrimental to the heart, vessels and kidneys, contributing to hypertension and the signs and progression of heart failure. Aldosterone secretion, abnormally elevated in heart failure and hypertension, can be blunted with angiotensin-converting enzyme inhibitors. Amlodipine, used to treat hypertension and heart failure, was hypothesized to activate the renin-angiotensin-aldosterone system (RAAS). A study was conducted with six normal adult male beagle dogs. Each dog received amlodipine (0.57 mg/kg b.i.d.) for 6 days, followed by amlodipine (0.57 mg/kg b.i.d.) and enalapril (0.57 mg/kg b.i.d.) for 4 days. Blood pressure, heart rate, serum chemistries and urinary aldosterone excretion, as a measure of RAAS activation, were compared with baseline values. Blood pressure fell by approximately 7% with amlodipine (P = 0.05) and a further 7% with the combination of amlodipine and enalapril (P < 0.01). Blood urea nitrogen increased with the combination (P < 0.05) but only one dog became mildly azotemic. Renin-angiotensin-aldosterone system activation, based on 24 h urinary aldosterone excretion and by aldosterone:creatinine ratio was increased by approximately threefold (P < 0.05) with amlodipine administration. This effect was blunted by enalapril, such that aldosterone excretion was no longer different from that observed under control conditions, although values for 24-h aldosterone excretion did not return to pretreament levels.  相似文献   

8.
The effect of renal insufficiency was studied on the pharmacokinetics (PK) and pharmacodynamics (PD) of the angiotensin-converting enzyme (ACE) inhibitor benazepril in cats. The active metabolite of benazepril, benazeprilat, is eliminated principally ( approximately 85%) via biliary excretion in cats. A total of 20 control animals and 32 cats with moderate renal insufficiency induced by partial nephrectomy were used. Assessments were made at steady state after treatment with placebo or benazepril (0.25-2 mg/kg) once daily for a minimum of 10 days. The PK endpoint was the AUC (0-->24 h) of total plasma benazeprilat. The PD endpoints were systolic, diastolic and mean blood pressures (respectively SBP, DBP and MBP) measured by telemetry, and plasma ACE activity, assessed by an ex vivo assay. Renal function was assessed by glomerular filtration rate (GFR), measured by inulin clearance, and plasma creatinine concentrations (1/PCr). As compared with control animals, the renal insufficient cats had a 78% reduction in GFR (0.57 +/- 0.41 mL/min kg), increased plasma creatinine (2.7 +/- 1.0 mg/dL), urea (44.0 +/- 11.9 mg/dL) and ACE activity, and moderately increased blood pressure (SBP 171.8 +/- 5.1 mmHg) (all parameters P < 0.05). Renal insufficient cats receiving benazepril had significantly (P < 0.05) lower SBP, DBP, MBP and ACE, and higher GFR values as compared with placebo-treated animals. There were no significant differences in SBP, DBP, MBP, benazeprilat or ACE values according to the degree of renal insufficiency in cats receiving benazepril. It is concluded that no dose adjustment of benazepril is necessary in cats with moderate renal insufficiency.  相似文献   

9.
The disposition and effect of benazepril and its active metabolite, benazeprilat, were evaluated in cats using a pharmacokinetic/pharmacodynamic model. Cats received single 1 mg/kg doses of intravenous 14C-benazeprilat and oral 14C-benazepril.HCl, and single and repeat (eight daily) oral administrations of 0.25, 0.5 and 1.0 mg/kg nonlabelled benazepril.HCl. The pharmacokinetic endpoints were plasma concentrations of benazepril and benazeprilat, and recovery of radioactivity in faeces and urine. The pharmacodynamic endpoint was plasma angiotensin-converting enzyme (ACE) activity. Benazeprilat data were fitted to an equation corresponding to a single-compartment model with a volume equal to the blood space (Vc = 0.093 L/kg). Within this space, benazeprilat was bound nonlinearly to ACE, which was mainly tissular (89.4%) rather than circulating (10.6%). Free benazeprilat was eliminated quickly from the central compartment (t1/2 approximately 1.0 h; Cl approximately 0.125 L/kg/h), elimination being principally biliary ( approximately 85%) rather than urinary ( approximately 15%). Nevertheless, inhibition of ACE was long-lasting (t1/2 16-23 h) due to high affinity binding of benazeprilat to ACE (Kd approximately 3.5 mmol/L, IC50 approximately 4.3 mmol/L). Simulations using the model predict a lack of proportionality between dose of benazepril, plasma benazeprilat concentrations and effect due to the nonlinear binding of benazeprilat to ACE. For example, increasing the dose of benazepril (e.g. above 0.125 mg/kg q24 h) produced only small incremental inhibition of ACE (either peak effect or duration of action).  相似文献   

10.
Enalapril is an angiotensin converting enzyme (ACE) inhibitor that is frequently used in human, feline and canine patients with cardiac disease. Its use has been associated with impotence in human patients. The purpose of this study was to evaluate if enalapril (0.5 mg/kg PO, q24h) is likely to alter behavior in stallions and to assess its effect on ACE activity at the standard dose used in dogs and cats. Twelve pony stallions were evaluated by physical examination and echocardiography followed by treatment with enalapril (n = 6) or placebo (n = 6) for 2 months. After one month, blood was drawn and stored to evaluate ACE activity in the 2 groups. At the end of the study, repeat physical examination and echocardiography were performed. Physical examination, echocardiographic indices, and reproductive performance were unchanged and there was no suppression of ACE activity. Results of this study suggest that enalapril (0.5 mg/kg PO, q24h) is either poorly absorbed in the horse or is inadequately converted to the active form of the drug, enalaprilat.  相似文献   

11.
The pharmacokinetics of ramipril and its active metabolite, ramiprilat, was determined in cats following single and repeated oral doses of ramipril (Vasotop® tablets) (once daily for 9 days) at dose rates of 0.125, 0.25, 0.5 and 1.0 mg/kg. The pharmacodynamic effects were assessed by measuring plasma angiotensin-converting enzyme (ACE) activity. Maximum ramipril concentrations were attained within 30 min following a single dose and declined rapidly (concentrations were below the limit of quantification 4 h after treatment). Peak ramiprilat concentrations were detected at approximately 1.5 h. The apparent terminal half-life ( t ½ β ) was ≥20 h irrespective of the dose. Ramiprilat accumulated in plasma (ratio of accumulation 1.3 to 1.9 depending on the dose rate) following repeated administration. Steady-state conditions were attained after the second dose. Excretion was predominant in faeces (87%) and to a lesser extent in urine (11%). The rate and extent of absorption of ramipril as well as its conversion to ramiprilat were not significantly influenced by the presence of food in the gastrointestinal tract. Plasma-ACE activity was almost completely abolished 0.5–2.0 h after treatment, irrespective of the dose rate. Significant inhibition of ACE activity of 54.7 to 82.6% (depending on the dosage) was still present 24 h after treatment. Treatment was well-tolerated in all cats. Ramipril at a dose rate of 0.125 mg/kg once daily produces significant and long-lasting inhibition of ACE activity in healthy cats. The appropriateness of this dosage regime needs to be confirmed in diseased cats.  相似文献   

12.
This study investigated the potential for nephrotoxicity of gentamicin in cats by measuring marker enzyme concentrations, [Na], [K], osmolality, and pH of the urine, and blood urea nitrogen (BUN) levels. Gentamicin was administered i.m. at 4.4 mg/kg once daily (s.i.d.) or twice daily (b.i.d.) for 7 days. Concentrations of lactic dehydrogenase (LDH), lysozyme (LZM), alkaline phosphatase (AP), and glutamate dehydrogenase (GD) were measured as total 24-h excretions. The s.i.d. regimen produced only a slight increase in LDH excretion after 5 days, whereas the b.i.d. regimen caused an increase in the excretion of all enzymes. The greatest elevations were observed for LZM and LDH. Of the enzymes studied, these appeared to be the most appropriate to monitor for potential nephrotoxicity, except that urinary concentrations did not correlate well with duration of gentamicin administration. Only slight elevations in BUN were observed for either regimen. Single daily administration increased urine osmolality slightly, but b.i.d. treatment caused a marked and immediate decrease in urine osmolality, [Na], and total Na excretion. Urinary [K] was also depressed, as was total K excretion after 6 days. Urine pH was not substantially affected. This study showed that the recommended daily dose of 4.4 mg/kg produced little if any evidence of nephrotoxicity as indicated by the parameters measured. Twice daily dosing, however, produced elevations in urine enzyme concentrations, and markedly decreased urine osmolality and Na and K excretion. Compared to other species studied, the cat appears particularly sensitive to urine concentrating alterations resulting from repeated gentamicin administration.  相似文献   

13.
This study was designed to determine the degree of inhibition of the angiotensin-converting enzyme (ACE) in 5 normal dogs given single doses of conventionally used ACE inhibitors (ACEis). In addition the time required for that inhibition to return to 50% of the difference between maximum and zero (control values) was measured as an estimate of duration of action. The 5 ACEis (with dosages given in parentheses) were bena/april (0.5 mg/kg), captopril (2.0 mg/kg), enalapril (0.5 mg/kg), lisinopril (0.5 mg/kg), and ramipril (0.25 mg/kg). Blood samples for ACE activities were obtained before dosing and at 1.5, 3.0, 6.0, 12.0, and 24.0 hours after dosing. All ACEis except captopril decreased ACE activities to approximately 25% of control by the 1.5-to 3.0-hour sample, and ACE activities returned to 50% of the difference by the 12-hour sample. The value of ACE activity returned to normal by 24 hours for benazapril, whereas values for ACE activity remained below normal for enalapril, lisinopril, and ramipril at 24 hours. For captopril, however, ACE levels decreased to approximately 80% of control by the 1.5-hour recording, and returned to levels not different from control by the 3-hour recording. Based upon this study performed on normal dogs given a single dose, no pharmacokinctic advantage or disadvantage is apparent for any ACEi except captopril, which, at the dosage used, decreased ACE levels to a much lesser degree and shorter time.  相似文献   

14.
OBJECTIVE: To determine the optimal dosage of clomipramine for the treatment of urine spraying in cats. DESIGN: Randomized controlled multicenter clinical trial. ANIMALS: 67 neutered cats. PROCEDURE: Cats with a minimum 1-month history of spraying urine against vertical surfaces at least twice per week were randomly assigned to be treated with a placebo or with clomipramine at a dosage of 0.125 to 0.25 mg/kg (0.057 to 0.11 mg/lb), 0.25 to 0.5 mg/kg (0.11 to 0.23 mg/lb), or 0.5 to 1 mg/kg (0.23 to 0.45 mg/lb), p.o., every 24 hours for up to 12 weeks. Owners of all cats were given information on behavioral treatment and environmental modification. RESULTS: Prior to treatment, mean number of urine spraying events ranged from 0.9 to 1.3 urine spraying events/d for the 4 groups, and mean percentage of days with urine spraying events ranged from 62% to 69%. All 3 dosages of clomipramine were associated with significant reductions in frequency of urine spraying. Sedation was the most common adverse effect and was identified in 27 of the 50 cats treated with clomipramine; however, treatment was not discontinued in any cat because of sedation. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the present study suggest that compared with a placebo, clomipramine significantly reduces the frequency of urine spraying in cats in terms of the number of urine spraying events per day and the number of days with urine spraying events. For cats with urine spraying, the recommended initial dosage of clomipramine is 0.25 to 0.5 mg/kg, p.o., every 24 hours.  相似文献   

15.
Pregnant sows were injected subcutaneously (s.c.) or intramuscularly (i.m.) with a barium selenate suspension (0.5–1.0 mg Se/kg body weight (b.w.)) and together with control animals fed a commercial diet. No response to the injection was seen either in blood selenium levels or in glutathione peroxidase (GSH-Px) activity in the sows. There was, however, a significant difference in these parameters between piglets born from treated dams and control animals. This status was maintained during the nursing period. In another experiment pigs (20 kg b.w.) on a Se-deficient diet were injected s.c. and i.m. with barium selenate (2.5 mg Se/kg b.w.). The treated groups maintained their blood levels of selenium and GSH-Px activity, although the selenium values in the group treated intramuscularly started to decline after 4 weeks. Organ samples from both groups were equal with regard to selenium at the time of slaughter while the control group showed a rapid decline both in blood selenium levels and GHS-Px activity.  相似文献   

16.
Pharmacokinetic and pharmacodynamic of IV enalapril at 0.50 mg/kg, PO placebo and PO enalapril at three different doses (0.50, 1.00 and 2.00 mg/kg) were analyzed in 7 healthy horses. Serum concentrations of enalapril and enalaprilat were determined for pharmacokinetic analysis. Angiotensin-converting enzyme (ACE) activity, serum ureic nitrogen (SUN), creatinine and electrolytes were measured, and blood pressure was monitored for pharmacodynamic analysis.  相似文献   

17.
Twelve pigs were randomly assigned to 1 of 2 groups, droperidol or midazolam, to determine a sedative dose of each drug that would facilitate handling of the pigs. Each pig in the group received all of the test doses with 5-7 d between treatments (droperidol--0.1, 0.3, 0.6 mg/kg, or midazolam--0.25, 0.5, 1.0 mg/kg) and saline (3 mL), i.m. One investigator, unaware of the treatment administered, assessed the time of onset, degree, and duration of sedation. The 0.3 mg/kg dose of droperidol and 0.5 mg/kg dose of midazolam were judged to be the most suitable for sedation and produced similar degrees of sedation, although the onset and duration of sedation was significantly longer for the droperidol group. The effects of these 2 doses on heart rate, respiratory rate, systolic blood pressure, and rectal temperature were assessed in 12 pigs randomly assigned to 1 of the 2 treatments. Respiratory rate decreased significantly with droperidol at 10, 15, and 30 min. Temperature was significantly decreased at 60 min following midazolam. This study demonstrates that 0.3 mg/kg i.m. of droperidol and 0.5 mg/kg i.m. of midazolam induce adequate sedation in pigs with minimal cardiorespiratory changes.  相似文献   

18.
The aim of this study was to determine the contribution of alpha 2- and alpha 1-adrenoceptor agonist activity of the formamidine, amitraz, on peripheral circulation in the dog. Intra-arterial injections of amitraz (0.25-5.0 micrograms/kg) produced a dose-dependent increase in perfusion pressure in the autoperfused hind limbs of methoxyflurane-anaesthetized dogs. A constant blood flow to the hind limbs was maintained using a peristaltic pump. Intravenous phentolamine (0.5 mg/kg), prazosin (35 micrograms/kg) and yohimbine (10 micrograms/kg) in separate experiments antagonized the vasoconstrictor actions of amitraz and produced a parallel shift to the right of the amitraz dose-response curve. Cumulative doses of amitraz (0.5-15 micrograms/kg) given by intracisterna magna (i.c.m.) injections reduced mean arterial pressure and heart rate in a dose-dependent manner. Similar responses were produced by intravenous amitraz but at much higher doses. In separate experiments amitraz-induced hypotension (doses up to 25 micrograms/kg i.c.m.) was prevented by pre-treatment with yohimbine (30 micrograms/kg i.c.m.) but not prazosin (20 micrograms/kg i.c.m.). Both antagonists partially inhibited the bradycardia produced by amitraz. It is concluded that amitraz stimulates alpha 1- and alpha 2-adrenoceptors to produce vascular constriction. The central hypotensive action of amitraz appears to be mediated by alpha 2-adrenoceptors; however, both receptor subtypes appear to be stimulated to produce bradycardia.  相似文献   

19.
Following a single oral dose of trimethoprim (10 mg/kg b. wt.) in normal fowls, the highest serum concentration achieved 4 hours post-administration with value of 0.64 microgram/ml. The absorption half-life time was 0.64 hours. The elimination half life was 4.73 hours. During repeated oral administration of 10 mg/kg b. wt., once daily for five consecutive days, trimethoprim peaked in serum, 4 h after each dose. Trimethoprim persisted in all fowl's tissues for 96 hours after stopping of drug administration. After oral administration of josamycin (18 mg/kg b. wt.) and trimethoprim (10 mg/kg b. wt.) in normal fowls, a maximum serum concentration of trimethoprim was recorded at 2 hours with half-life of absorption (t0.5(ab)) valued 0.74 hour. The elimination half-life (t0.5 beta) was 4.37 hours. During repeated oral administration of josamycin (18 mg/kg b. wt.) and trimethoprim (10 mg/kg b. wt.) once daily for five consecutive days in normal fowls, the highest plasma concentrations of trimethoprim occurred 2 hours post each dose. The daily maximum plasma concentrations during the repeated oral administration of both tested drugs were nearly constant.  相似文献   

20.
The onset of action and behavioural effects following intravenous (i.v.) and intramuscular (i.m.) administration of 0.05, 0.5, 1.0, 2.0 and 5.0 mg/kg of midazolam were studied for 2 h in 20 awake, healthy cats. All cats, except one that received 0.05 mg/kg i.m., showed effects of the drug, whereas no effects were observed in cats administered only the vehicle in which midazolam was dissolved. The onset of action was rapid following both i.v. and i.m. administration, some cats became ataxic, while others assumed positions of sternal or lateral recumbency. Even after administration of the highest dose (5.0 mg/kg), anaesthesia was not induced, with swallowing reflexes and conscious perception of a clamp placed on the tail still present in all cats. An abnormal arousal state was observed in many cats after administration of midazolam. During the first hour, restlessness was more commonly observed, while from 1 to 2 h, sedation was more prominent in cats that received the highest dose. Ataxia occurred in all but one cat, was short-lived in cats that received the lower doses, but still present at 2 h in all cats that received 2.0 and 5.0 mg/kg. Midazolam caused some of the cats to behave differently when approached and restrained compared with behavioural patterns identified prior to administration of the drug. The cats were more likely to behave abnormally following i.v. administration rather than i.m. administration and, for the most part, abnormal behaviour was equally distributed between the two extremes; cats being easier to approach and restrain and cats being more difficult to approach and restrain. Food consumption increased significantly, during the 2 h period, following all i.m. doses and all but the highest (5.0 mg/kg) i.v. dose, with most of the food being consumed in the first hour after administration.  相似文献   

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