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1.
The vehicle in which endectocide compounds are formulated plays a relevant role in their absorption kinetics and resultant systemic availability. The pharmaceutical bioequivalence and comparative plasma disposition kinetics of ivermectin (IVM), following the subcutaneous administration of two injectable formulations to pigs and cattle were investigated using parallel experimental designs. Sixteen parasite-free male Duroc Jersey-Yorkshire crossbred pigs (90-110 kg) (Expt 1) and 16 parasite-free male Holstein calves (100-120 kg) (Expt 2) were divided into two groups and treated subcutaneously at either 300 (pigs) or 200 (calves) microg/kg with two different propylene glycol/glycerol formal (60: 40) based IVM formulations; in both experiments pigs or calves in Group A received the test (IVM-TEST) formulation and those in Group B were treated with the reference formulation (IVM-CONTROL). Heparinized blood samples were taken from 0 h up to either 20 (pigs) or 30 (calves) days post-treatment and plasma was extracted, derivatized and analysed by high performance liquid chromatography (HPLC) using fluorescence detection. Early detection of IVM (12 h) with a peak plasma concentration (C(max)) between 33 and 39 ng/mL was observed in pigs. The drug was detected in plasma up to 20 days post-administration of either formulation, resulting in elimination half-lives between 3.47 and 3.80 days. There were no differences between the IVM-TEST and IVM-CONTROL formulations in the kinetic parameters (except t(max)) obtained in pigs. IVM was detected in plasma between 12 h and 30 days post-administration of both formulations under investigation in cattle. The plasma disposition kinetics of IVM in calves was similar following treatment with both formulations. C(max) values (between 40.5 and 46.4 ng/mL) were achieved at 2 days post-administration of both formulations. None of the estimated kinetic parameters were statistically different between drug formulations. The injectable IVM formulations investigated were bioequivalent after their subcutaneous administration to both pigs and calves at recommended dose rates.  相似文献   

2.
Doxycycline hyclate (DOX-h) can be regarded as a time-dependant antibacterial. Hence, a parenteral long-acting formulation may be regarded as more pharmacologically sound. A poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its s.c. injection to calves. Serum concentrations profiles for such a prepartion were compared to the corresponding profiles obtained with an aqueous formulation of DOX-h injected either i.m. or i.v. in 10 calves in a crossover study at dose of 10mg/kg, with washout periods. DOX-h-LA showed the greatest values for bioavailability (602%); maximum serum concentration (C(max)) value was 1.99microg/mL with a time to reach C(max) (T(max)) of 25h and an elimination half-life of 40.81h. Considering minimum effective serum concentration of 0.5microg/mL a dose-interval of 80h can be achieved for DOX-h-LA, and only 9.7h and 17h after the i.v. or i.m. administration of DOX-h, respectively.  相似文献   

3.
The pharmacokinetics of marbofloxacin were investigated in healthy (n=8) and Mannheimia haemolytica naturally infected (n=8) Simmental ruminant calves following intravenous (i.v.) and intramuscular (i.m.) administration of 2 mg kg(-1) body weight. The concentration of marbofloxacin in plasma was measured using high performance liquid chromatography with ultraviolet detection. Following i.v. administration of the drug, the elimination half-life (t(1/2 beta)) and mean residence time (MRT) were significantly longer in diseased calves (8.2h; 11.13 h) than in healthy ones (4.6 h; 6.1 h), respectively. The value of total body clearance (CL(B)) was larger in healthy calves (3 ml min(-1) kg(-1)) than in diseased ones (1.3 ml min(-1) kg(-1)). After single intramuscular (i.m.) administration of the drug, the elimination half-life, mean residence time (MRT) and maximum plasma concentration (C(max)) were higher in diseased calves (8.0, 12 h, 2.32 microg ml(-1)) than in healthy ones (4.7, 7.4 h, 1.4 microg ml(-1)), respectively. The plasma concentrations and AUC following administration of the drug by both routes were significantly higher in diseased calves than in healthy ones. Protein binding of Marbofloxacin was not significantly different in healthy and diseased calves. The mean value for MIC of marbofloxacin for M. haemolytica was 0.1+/-0.06 microg ml(-1). The C(max)/MIC and AUC(24)/MIC ratios were significantly higher in diseased calves (13.0-64.4 and 125-618 h) than in healthy calves (8-38.33 and 66.34-328 h). The obtained results for surrogate markers of antimicrobial activity (C(max)/MIC, AUC/MIC and T > or = MIC) indicate the excellent pharmacodynamic characteristics of the drug in diseased calves with M. haemolytica, which can be expected to optimize the clinical efficacy and minimize the development of resistance.  相似文献   

4.
The pharmacokinetic behavior of marbofloxacin was studied in goats after single-dose subcutaneous (SC) administration of 2mg/kg bodyweight. Drug concentration in plasma was determined by high performance liquid chromatography and the data obtained were subjected to non-compartmental kinetic analysis. Marbofloxacin peak plasma concentration (C(max)=1.77+/-0.24microg/mL) was reached 1.25+/-0.50h (T(max)) after SC administration. The elimination half-life (t(1/2beta)) and area under curve (AUC) were 5.74+/-1.21h and 8.15 vs 2.33microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, it was concluded that a SC dose of 2mg/kg/24h of marbofloxacin could be adequate to treat infections caused by high susceptible bacteria like Escherichia coli or Salmonella spp.  相似文献   

5.
The study evaluated the pharmacokinetics of tramadol and its major metabolites O-desmethyltramadol (M1), N-desmethyltramadol (M2) and N-O didesmethyltramadol (M5) following a single oral administration of a sustained release (SR) 100mg tablet to dogs. Plasma tramadol concentration was greater than the limit of quantification (LOQ) in three dogs, M1 was quantified only in one dog while M2 and M5 were quantified in all of the dogs. The median values of C(max) (maximum plasma concentration), T(max) (time to maximum plasma concentration) and T(1/2) (half-life) for tramadol were 0.04 (0.17-0.02)mirog mL(-1), 3 (4-2) and 1.88 (2.211-1.435)h, respectively. M5 showed median values of C(max), T(max) and T(1/2) of 0.1 (0.19-0.09)microg mL(-1), 2 (3-1) and 4.230 (6.583-1.847)h, respectively. M2 showed median values of C(max), T(max) and T(1/2) of 0.22 (0.330-0.080)microg mL(-1), 4 (7-3) and 4.487 (6.395-1.563)h, respectively. The findings suggest that the SR formulation of tramadol may not have suitable pharmacokinetic characteristics to be administered once-a-day as an effective and safe treatment for pain in the dog.  相似文献   

6.
Pharmacokinetic variables of fosfomycin were determined after administration of buffered disodium-fosfomycin intravenously (IV), intramuscularly (IM), subcutaneously (SC) and orally (PO), in mongrel dogs, at 40 and 80 mg/kgday for three days. Renal integrity was also assessed by measuring key serum variables. Day 1, day 2 and day 3 plasma concentration vs. time profiles were undistinguishable, but there appears to be a lineal increase in serum concentrations vs. time with the dose. A non-accumulative kinetic behavior was observed after three days with both doses and most pharmacokinetic variables remain unaltered. Considering a MIC range from 1 mirog/mL to 16 microg/mL of fosfomycin in serum for sensitive bacteria, and a negligible plasma protein binding of fosfomycin (<0.5%), useful plasma concentrations can only be achieved after the SC injection of 80 mg/kg every 12h, having a C(max)=18.96+/-0.3 microg/mL; a T(1/2beta)=2.09+/-0.06 microg/mL and a bioavailability of 84-85%. No alterations were observed in serum variables of kidney-related biochemical values.  相似文献   

7.
The pharmacokinetic profile of avermectin and milbemycin compounds is affected by different drug- and host-related factors. This work reports the influence of cattle breeds on the plasma kinetics of moxidectin (MXD) after topical (pour-on) administration. Parasite-free Aberdeen Angus and Holstein calves were treated with a commercial MXD pour-on formulation at 500 microg/kg. Blood samples were collected over a period of 35 days post-treatment and the recovered plasma was analysed by high performance liquid chromatography using fluorescence detection. MXD was detected in plasma from two hours up to 35 days post-treatment in animals from both breeds. A slow MXD absorption and delayed peak plasma concentration were observed in Aberdeen Angus compared to Holstein calves. Significant lower systemic availability (expressed as AUC) (P<0.01) and peak plasma concentration (C(max)) (P<0.05) were also observed in Aberdeen Angus calves, although the plasma mean residence time (MRT) and elimination half-lives (T(1/2el)) of MXD in both breeds were similar. The pharmacokinetic differences observed between cattle breeds contribute to explain the variability in the pattern of clinical efficacy for pour-on administered endectocide compounds reported in different field trials.  相似文献   

8.
The pharmacokinetic properties of ceftazidime, a third generation cephalosporin, were investigated in five cats after single intravenous (IV) and intramuscular (IM) administration at a dose rate of 30 mg/kg. Minimum inhibitory concentrations (MICs) of ceftazidime for some Gram-negative (Escherichia coli, n=11) and Gram-positive (Staphylococcus spp., n=10) strains isolated from clinical cases were determined. An efficacy predictor, measured as the time over which the active drug exceeds the bacteria minimum inhibitory concentration (T>MIC), was calculated. Serum ceftazidime disposition was best fitted by a bi-compartmental and a mono-compartmental open model with first-order elimination after IV and IM dosing, respectively. After IV administration, distribution was rapid (t(1/2(d)) 0.04+/-0.03 h), with an area under the ceftazidime serum concentration:time curve (AUC((0-infinity))) of 173.14+/-48.69 microg h/mL and a volume of distribution (V((d(ss)))) of 0.18+/-0.04 L/kg. Furthermore, elimination was rapid with a plasma clearance of 0.19+/-0.08 L/hkg and a t(1/2) of 0.77+/-0.06 h. Peak serum concentration (C(max)), T(max), AUC((0-infinity)) and bioavailability for the IM administration were 89.42+/-12.15 microg/mL, 0.48+/-0.49 h, 192.68+/-65.28 microg h/mL and 82.47+/-14.37%, respectively. Ceftazidime MIC for E. coli ranged from 0.0625 to 32 microg/mL and for Staphylococcus spp. from 1 to 64 microg/mL. T>MIC was in the range 35-52% (IV) and 48-72% (IM) of the recommended dosing interval (8-12h) for bacteria with a MIC(90)4 microg/mL.  相似文献   

9.
The present study was planned to investigate the plasma disposition kinetics and the pattern of moxifloxacin elimination in the milk of lactating ewes (n=6) following a single intravenous (IV) bolus or intramuscular (IM) injections at a dosage of 5 mg/kg in all animals. A crossover study was carried out in two phases separated by 21 days. Plasma and milk samples were collected serially for 72 h and moxifloxacin concentrations were assayed using high performance liquid chromatography with fluorescence detection. A two-compartment open model best described the decrease of moxifloxacin concentration in the plasma after IV injection. The disposition after IM administration moxifloxacin was best described by a one-compartment model. Following IV administration, the distribution half-life (t(1/2alpha)) was 0.22+/-0.02 h. The elimination half-life was 1.77+/-0.23 h. The volume of distribution at steady state (V(dss)) was 0.84+/-0.12L/kg, the total body clearance (Cl(tot)) was 0.34+/-0.04 L/h/kg and the area under the curve (AUC) was 14.74+/-2.16 microg h/mL. Following IM administration, the mean T(max), C(max), t(1/2el) and AUC values for plasma data were 1.45+/-0.02 h, 2.21+/-0.27 microg/mL, 2.68+/-0.19 h and 14.21+/-2.35 microg h/mL. The IM bioavailability was 96.35+/-17.23% and the in vitro protein binding of moxifloxacin ranged from 32-37%. Penetration of moxifloxacin from the blood into milk was rapid and extensive, and the moxifloxacin concentrations in milk exceeded those in plasma from 1h after administration. The kinetic values AUC(milk)/AUC(plasma) and C(maxmilk)/C(maxplasma) ratios indicated a wide penetration of moxifloxacin from the bloodstream to the mammary gland. The in vitro minimum inhibitory concentration (MIC) of moxifloxacin for Mannheimia haemolytica was found to be 0.035 microg/mL.  相似文献   

10.
The comparative concentration profiles of the (+) and (-) albendazole sulphoxide (ABZSO) enantiomers obtained in plasma and in selected target tissues/fluids after intravenous (i.v.) administration of a racemic formulation of ricobendazole (RBZ) to cattle were characterised. Fourteen Holstein calves received RBZ (racemic solution, 150 mg/mL) by i.v. administration at 7.5 mg/kg. Jugular blood samples were collected over 48 h post-treatment (plasma kinetic trial) and two animals were sacrificed at either 4, 12, 20, 28 or 32 h post-treatment to obtain samples of abomasal/small intestine mucosal tissue, abomasal/small intestine fluids, bile, liver and lung tissue (tissue distribution study). The (-)ABZSO enantiomer was depleted significantly faster from plasma compared with the (+)ABZSO antipode. The plasma AUC for (+)ABZSO (38.3 microg. h/mL) was significantly higher (P < 0.05) compared with that obtained for (-)ABZSO (20.5 microg. h/mL). The (+)ABZSO enantiomer was the predominant antipode measured in bile, abomasal fluid and abomasal mucosa. For instance, at 12 h post-treatment the (+)/(-) concentration ratios were: 12.9 (plasma), 1.62 (abomasal mucosa), 13.0 (abomasal fluid), 2.92 (intestinal mucosa), 9.87 (intestinal fluid) and 21.5 (bile). No marked differences between the concentration profiles of both enantiomers were observed in the liver tissue. Albendazole (ABZ) was recovered from the liver, lung and gastrointestinal (GI) mucosal tissues of RBZ-treated calves up to 32 h post-treatment, probably produced by a GI microflora-mediated sulphoreduction of RBZ. An enantioselective kinetic behaviour may account both for the faster depletion of the (-) enantiomer and for the higher availabilities of the (+) antipode observed in plasma and in most of the tissues/fluids investigated. The simultaneous evaluation of the plasma kinetics and tissue concentration profiles of both enantiomeric forms reported here, may help to interpret the relationship between chiral behaviour and pharmacological action for sulphoxide derivatives of benzimidazole (BZD) methylcarbamate anthelmintics.  相似文献   

11.
The pharmacokinetic behaviour of enrofloxacin in greater rheas was investigated after intramuscular (IM) administration of 15 mg/kg. Plasma concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were determined by high performance liquid chromatography. Enrofloxacin peak plasma concentration (C(max)=3.30+/-0.90 microg/mL) was reached at 24.17+/-9.17 min. The terminal half-life (t(1/2lambda)) and area under the curve (AUC) were 2.85+/-0.54 h and 4.18+/-0.69 microg h/mL, respectively. The AUC and C(max) for ciprofloxacin were 0.25+/-0.06 microg/mL and 0.66+/-0.16 microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, an IM dose of 15 mg/kg of enrofloxacin would appear to be adequate for treating infections caused by highly susceptible bacteria (MIC(90)<0.03 microg/mL) in greater rheas.  相似文献   

12.
Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstrating that ABZ was completely metabolised by first-pass mechanisms in donkeys. Maximum plasma concentrations (C(max)) of FBZSO (0.49microg/mL) and FBZSO(2) (0.60microg/mL) were detected at (t(max)) 5.67 and 8.00h, respectively, following administration of FBZSO. The area under the curve (AUC) of the sulphone metabolite (10.33microg h/mL) was significantly higher than that of the parent drug FBZSO (5.17microg h/mL). C(max) of albendazole sulphoxide (ABZSO) (0.08g/mL) and albendazole sulphone (ABZSO(2)) (0.04microg/mL) were obtained at 5.71 and 8.00h, respectively, following ABZ administration. The AUC of the sulphoxide metabolite (0.84microg h/mL) of ABZ was significantly higher than that of the sulphone metabolite (0.50microg h/mL). The highest dry-faecal concentrations of parent molecules were detected at 32, 34 and 30h for FBZSO, FBZ and ABZ, respectively. The sulphide metabolite was significantly higher than the parent molecule after FBZSO administration. The parent molecule was predominant in the faecal samples following FBZ administration. After ABZ administration, the parent molecule was significantly metabolised, probably by gastrointestinal microflora, to its sulphoxide metabolite (ABZSO) that showed a similar excretion profile to the parent molecule in the faecal samples. The AUC of the parent FBZ was significantly higher than that of FBZSO and ABZ in faeces. It is concluded that the plasma concentration of FBZSO was significantly higher than that of FBZ and ABZ. Although ABZ is not licensed for use in Equidae, its metabolites presented a greater plasma kinetic profile than FBZ which is licensed for use in horses. A higher metabolic capacity, first-pass effects and lower absorption of benzimidazoles in donkeys decrease bioavailability and efficacy compared to ruminants.  相似文献   

13.
This study was undertaken to characterize the population pharmacokinetics (PK), therapeutic dose, and preferred route of administration for pyrazinamide (PZA) in elephants. Twenty-three African (Loxodonta africana) and Asian (Elephas maximus) elephants infected with or in contact with others culture positive for Mycobacterium tuberculosis were dosed under treatment conditions. PZA was dosed daily at 20-30 mg/kg via oral (fasting or nonfasting state) or rectal (enema or suppository) administration. Blood samples were collected 0-24 h postdose. Population PK was estimated using nonlinear mixed effect modeling. Drug absorption was rapid with T(max) at or before 2 h regardless of the method of drug administration. C(max) at a mean dose of 25.6 (+/-4.6) mg/kg was 19.6 (+/-9.5 microg/mL) for PZA given orally under fasting conditions. Under nonfasting conditions at a mean dose of 26.1 +/- 4.2 mg/kg, C(max) was 25% (4.87 +/- 4.89 microg/mL) and area under concentration curve (AUC) was 30% of the values observed under fasting conditions. Mean rectal dose of 32.6 +/- 15.2 mg/kg yielded C(max) of 12.3 +/- 6.3 microg/mL, but comparable AUC to PZA administered orally while fasting. Both oral and rectal administration of PZA appeared to be acceptable and oral dosing is preferred because of the higher C(max) and lower inter-subject variability. A starting dose of 30 mg/kg is recommended with drug monitoring between 1 and 2 h postdose. Higher doses may be required if the achieved C(max) values are below the recommended 20-50 microg/mL range.  相似文献   

14.
Pharmacokinetics of florfenicol in North American elk (Cervus elaphus)   总被引：1，自引：0，他引：1  
Florfenicol pharmacokinetics after administration of a single subcutaneous (s.c.) dose of 40 mg/kg of body weight in adult elk (Cervus elaphus) was investigated. Serum florfenicol concentrations were determined by a sensitive high-performance liquid chromatographic method with limit of quantification of 0.03 microg/mL. Florfenicol pharmacokinetic parameters in elk were estimated using a noncompartmental approach. After a single s.c. injection, florfenicol concentrations remained above 1 microg/mL for approximately 36 h and above 0.5 microg/mL for approximately 72 h. Following s.c. injection, florfenicol was absorbed rapidly with a mean maximum concentration (C(max)) of 3.7 microg/mL achieved at 4.2 h (T(max)). The C(max) value in elk is similar to values reported in cattle at the same dose, suggesting that the 40 mg/kg s.c. dose achieves therapeutic concentrations in elk. A mean elimination half-life (t(1/2)) of 44 h is shorter than that reported in cattle. The more rapid elimination half-life in elk suggests that elk may require a multiple dose regimen for therapeutic success with s.c. Nuflor. We recommend s.c. Nuflor be administered subcutaneously to elk every 24 h at a dose level of 40 mg/kg.  相似文献   

15.
Ceftiofur sodium, a broad-spectrum cephalosporin, is active against gram-positive and gram-negative pathogens of veterinary importance. Two studies were designed to compare the intramuscular bioavailability of the current sodium salt and the new hydrochloride salt in pigs at doses of either 3 mg or 5 mg ceftiofur equivalents (CE)/kg body weight. Twenty-six healthy young pigs were selected for these two-period, two-treatment crossover studies, 12 for the 3 mg/kg study and 14 for the 5 mg/kg study. Each animal received one intramuscular (i.m.) injection of ceftiofur sodium and one i.m. injection of ceftiofur hydrochloride with a 14-day washout period between the two treatments. Blood samples were collected serially for up to 96 h postinjection. Plasma samples were then analysed using a validated assay that measures ceftiofur and all desfuroylceftiofur-related metabolites by high-performance liquid chromatography. In the 3 mg/kg dosage study, average maximum plasma concentration (C(max)) after administration of ceftiofur sodium was 15.8+/-3.40 microg/mL at 0.4-4 h after injection. After administration of ceftiofur hydrochloride, the C(max) was 11.8+/-1.67 microg/mL at 1-4 h after injection. Concentrations of ceftiofur and metabolites 72 h after the injection were 0.392+/-0.162 microg/mL for ceftiofur hydrochloride and 0.270+/-0.118 microg/mL for ceftiofur sodium. The mean area under the curve (AUC), from time 0 to the limit of quantitation (AUC(O-LOQ)) after ceftiofur hydrochloride administration, was 216+/-28.0 microg x h/mL, compared to 169+/-45.4 microg x h/mL after ceftiofur sodium administration. The calculated time during which plasma concentrations remained above 0.02 microg/mL (t(>0.2)) was 85.3+/-10.6 h for ceftiofur sodium and 77.2+/-10.7 h for ceftiofur hydrochloride. In the 5 mg/kg dosage study, C(max) after administration of ceftiofur sodium was 28.3+/-4.45 microg/mL at 0.33-2 h after injection. After administration of ceftiofur hydrochloride, the C(max) was 29.7+/-6.72 microg/mL at 0.66-2 h after injection. Concentrations of ceftiofur and metabolites 96 h after the injection were 0.274+/-0.0550 microg/mL for ceftiofur hydrochloride and 0.224+/-0.0350 microg/mL for ceftiofur sodium. The mean AUC(O-LOQ) after ceftiofur hydrochloride administration was 382+/-89.8 microg x h/mL compared to 302+/-54.4 microg x h/mL after ceftiofur sodium administration. The t(>0.2) was 78.9+/-9.65 h for ceftiofur sodium and 94.2+/-8.64 h for ceftiofur hydrochloride. Based on the similarity of the pharmacokinetic parameters of the sodium and hydrochloride formulations of ceftiofur, similar therapeutic efficacy can be inferred for the two products.  相似文献   

16.
The pharmacokinetic properties of marbofloxacin, a third generation fluoroquinolone, were investigated in six cats after single intravenous (IV) and repeat oral (PO) administration at a daily dose of 2 mg/kg. Marbofloxacin serum concentration was analysed by microbiological assay using Klebsiella pneumoniae ATCC 10031 as micro-organism test. Serum marbofloxacin disposition was best described by bicompartmental and mono-compartmental open models with first-order elimination after IV and oral dosing respectively. After IV administration, distribution was rapid (T(1/2(d)) 0.23+/-0.24 h) and wide, as reflected by the steady-state volume of distribution of 1.01+/-0.15 L/kg. Elimination from the body was slow with a body clearance of 0.09+/-0.02 L/h kg and a T(1/2) of 7.98+/-0.57 h. After repeat oral administration, absorption half-life was 0.86+/-1.59 h and T(max) of 1.94+/-2.11 h. Bioavailability was almost complete (99+/-29%) with a peak plasma concentration at the steady-state of 1.97+/-0.61 mug/mL. Drug accumulation was not significant after six oral administrations. Calculation of efficacy predictors showed that marbofloxacin has good therapeutic profile against Gram-negative and Gram-positive bacteria with a MIC(50) value <0.25 microg/mL.  相似文献   

17.
Two experiments were carried out to identify the target population of cattle for immunisation against East Coast fever (ECF) using the infection-and-treatment method. Firstly, a sentinel-calf study was used to determine the age window for ECF immunisation by determining ages at clinical detection of infection with Theileria parva. Six groups of five naive cross-bred (Bos taurus/Bos indicus) male calves, introduced at intervals of 2 months at a mean age of 26 days, were exposed to natural tick challenge on a high ECF-risk, small-holder farm in the coastal lowland, coconut-cassava agro-ecological zone of coastal Kenya. Secondly, a challenge study evaluated the relationship between the presence of T. parva antibodies and immunity. Ten indigenous adult Zebu cattle and nine Zebu young stock purchased from farmers in the same zone, and eight cross-bred calves (survivors of the sentinel-calf study) were challenged with 10 times the immunising dose of T. parva Marikebuni stock. Twenty-four of these 27 cattle had high antibody titres before challenge. Two cross-bred calves, obtained from an ECF-free area and seronegative to T. parva schizont antigen, also were challenged and used as susceptible controls. Twenty-five (83%) of the 30 sentinel calves contracted ECF over an age range of 36-116 days (mean 72 days). The remaining five calves died of other causes within 2 months of arrival on the farm. Fourteen of the 25 calves survived the infection and developed antibodies to T. parva. Despite tick control, seven of these 14 calves had a second episode of ECF and two died. In total, 13 of the 25 calves that contracted ECF died. Only one of 19 indigenous Zebu animals developed clinical ECF when challenged with T. parva Marikebuni (mild clinical signs with spontaneous recovery). Of the eight cross-bred survivors from the first experiment, only one succumbed to ECF when challenged and it died. Both susceptible cross-bred calves developed severe clinical signs of ECF and one died. The experimental studies show that in the high ECF-risk areas of the coconut-cassava zone of coastal Kenya, immunisation against ECF in cross-bred (B. taurus/B. indicus) cattle should be targeted at an early age (preferably within 1-2 months of birth).  相似文献   

18.
The pharmacokinetic properties and in vitro potency of nimesulide, a nonsteroidal anti-inflammatory drug (NSAID) were investigated in 8 or 10 dogs after intravenous (i.v.), intramuscular (i.m.) and oral (single and multiple dose) administrations at the nominal dose of 5 mg/kg. After i.v. administration, the plasma clearance was 15.3 +/- 4.2 mL/kg/h, the steady-state volume of distribution was low (0.18 +/- 0.011 L/kg) and the elimination half-life was 8.5 +/- 2.1 h. After i.m. administration, the terminal half-life was 14.0 +/- 5.3 h indicating a slow process of absorption with a maximum plasma concentration (6.1 +/- 1.5 microg/mL) at 10.9 +/- 2.1 h postadministration and the systemic bioavailability was 69 +/- 22%. After oral administration in fasted dogs, the maximal plasma concentration (10.1 +/- 2.7 microg/mL) was observed 6.1 +/- 1.6 h after drug administration, the plasma half-life was 6.2 +/- 1.9 h and the mean bioavailability was 47 +/- 12%. After daily oral administrations for 5 days, the average plasma concentration during the fifth dosage interval was 8.1 +/- 2.9 microg/mL and the overall bioavailability was 58 +/- 16%. The mean accumulation ratio was 1.27 +/- 0.4. In vitro nimesulide inhibitory potencies for cyclooxygenase (COX)-1 and COX-2 isoenzymes were determined using a whole blood assay. Canine clotting blood was used to test for inhibition of COX-1 activity and whole blood stimulated by lipopolysaccharide (LPS) was used to test for inhibition of COX-2 activity. The inhibitory concentration (IC50) for inhibition of COX-2 and COX-1 were 1.6 +/- 0.4 microM (0.49 +/- 0.12 microg/mL) and 20.3 +/- 2.8 microM (6.3 +/- 0.86 microg/mL) giving a nimesulide COX-1/COX-2 ratio of 12.99 +/- 3.41. It was concluded that at the currently recommended dosage regimen (5 mg/kg), the plasma concentration totally inhibits COX-2 and partly inhibits COX-1 isoenzyme.  相似文献   

19.
BACKGROUND: Commonly used dosage protocols for antimicrobial agents may alter the rate of gastric emptying. HYPOTHESIS: Parenteral administration of erythromycin increases and gentamicin decreases the rate of abomasal emptying. ANIMALS: Five male Holstein-Friesian calves (8-15 days of age). METHODS: Calves received each of the following 4 IM treatments in random order: control, 2 mL of 0.9% NaCl; erythromycin, 8.8 mg/kg; low-dose gentamicin, 4.4 mg/kg; high-dose gentamicin, 6.6 mg/kg. Abomasal emptying rate was assessed by acetaminophen and glucose absorption. Calves were fed 2 L of cow's milk containing acetaminophen (50 mg/kg body weight) 30 minutes after each treatment was administered, and jugular venous blood samples were obtained periodically after suckling. The maximum observed plasma acetaminophen concentration (actual C(max)) and time of actual C(max) (actual T(max)) were determined, and pharmacokinetic modeling was used to calculate model C(max) and model T(max). RESULTS: Erythromycin increased abomasal emptying rate, as indicated by a shorter time to actual T(max) and model T(max) (P < .05). Abomasal emptying rate after injection of low-dose gentamicin was similar to that of control. Administration of high-dose gentamicin resulted in a longer time to actual T(max) (P= .021) but did not change model T(max) (P= .62). CONCLUSIONS AND CLINICAL RELEVANCE: IM injection of erythromycin increased abomasal emptying rate in dairy calves, whereas low-dose and high-dose gentamicin did not alter the rate of abomasal emptying as measured by acetaminophen kinetics and glucose absorption. The clinical relevance of these findings remains to be determined.  相似文献   

20.
The purpose of this study was to establish the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in the plasma and interstitial fluid (ISF) following subcutaneous (s.c.) administration of enrofloxacin. Ultrafiltration probes were placed in the s.c. tissue, gluteal musculature, and pleural space of five calves. Each calf received 12.5 mg/kg of enrofloxacin. Plasma and ISF samples were collected for 48 h after drug administration and analyzed by high pressure liquid chromatography. Plasma protein binding of enrofloxacin and ciprofloxacin was measured using a microcentrifugation system. Tissue probes were well tolerated and reliably produced fluid from each site. The mean +/- SD plasma half-life was 6.8 +/- 1.2 and 7.3 +/- 1 h for enrofloxacin and ciprofloxacin, respectively. The combined (ciprofloxacin + enrofloxacin) peak plasma concentration (Cmax) was 1.52 microg/mL, and the combined area under the curve (AUC) was 25.33 microg/mL. The plasma free drug concentrations were 54% and 81% for enrofloxacin and ciprofloxacin, respectively, and free drug concentration in the tissue fluid was higher than in plasma. We concluded that Cmax/MIC and AUC/MIC ratios for free drug concentrations in plasma and ISF would meet suggested ratios for a targeted MIC of 0.06 microg/mL.  相似文献   

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