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1.
The in vitro antimicrobial activities of aditoprim (AP), a new dihydrofolate reductase (DHFR) inhibitor, trimethoprim (TMP), sulfadimethoxine (SDM), sulfamethoxazole (SMX), and combinations of these drugs against some porcine respiratory tract pathogens were determined by use of an agar dilution method. The minimal inhibitory concentrations (MIC) of these agents were determined twice against Bordetella bronchiseptica (n = 10), Pasteurella multocida (n = 10), and Actinobacillus pleuropneumoniae (n = 20) strains isolated from pigs suffering from atrophic rhinitis or pleuropneumonia. All B bronchiseptica strains were resistant to AP and TMP. The MIC50 values of AP and TMP for P multocida were 0.25 and 0.06 microgram/ml, respectively, and for A pleuropneumoniae, 1 and 0.25 microgram/ml, respectively. The MIC50 values of SDM and SMX for B bronchiseptica were 4 and 1 micrograms/ml, respectively; for P multocida, 16 and 8 micrograms/ml, respectively; and for A pleuropneumoniae, 16 and 8 micrograms/ml, respectively. The investigated combinations of the DHFR inhibitors and the selected sulfonamides had synergism for the A pleuropneumoniae strains; the MIC90 values of the combinations were less than or equal to 0.06 microgram/ml. Potentiation was not observed for the B bronchiseptica and the P multocida isolates. The MIC of the combinations against B bronchiseptica and P multocida corresponded respectively to the concentrations of the sulfonamides and the DHFR inhibitors in the combinations. For A pleuropneumoniae, 2 types of strains were used (25% of serotype 2 and 75% of serotype 9). Type-2 strains had lower susceptibility than type-9 strains to AP and TMP as well as to SDM and SMX (at least a fourfold difference in MIC between the 2 types of strains).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

2.
The pharmacokinetics were studied of sulfadimethoxine (SDM) or sulfamethoxazole (SMX) in combination with trimethoprim (TMP) administered as a single oral dose (25 mg + 5 mg per kg body weight) to two groups of 6 healthy pigs. The elimination half-lives of SMX and TMP were quite similar (2–3 h); SDM had a relatively long half-life of 13 h. Both sulfonamides (S) were exclusively metabolized to N4-acetyl derivatives but to different extents. The main metabolic pathway for TMP was O-demethylation and subsequent conjugation. In addition, the plasma concentrations of these drugs and their main metabolites after medication with different in-feed concentrations were determined. The drug (S:TMP) concentrations in the feed were 250:50, 500:100, and 1000:200 mg per kg. Steady-state concentrations were achieved within 48 h of feed medication, twice daily (SDM+TMP) or three times a day (SMX+TMP). Protein binding of SDM and its metabolite was high (>93%), whereas SMX, TMP and their metabolites showed moderate binding (48–75%). Feed medication with 500 ppm sulfonamide combined with 100 ppm TMP provided minimum steady-state plasma concentrations (C ss,min) higher than the concentration required for inhibition of the growth of 90% of Actinobacillus pleuropneumoniae strains (n = 20).  相似文献   

3.
The pharmacokinetics of two sulfonamide/trimethoprim combinations were investigated after intravenous administration to clinically healthy pigs and to the same pigs following a challenge with Actinobacillus pleuropneumoniae toxins. Endobronchial challenge with A.pleuropneumoniae toxins resulted in fever, increased white blood cell counts and decreased water and feed consumption. Healthy, as well as febrile, pigs were given sulfadimethoxine (SDM) or sulfamethoxazole (SMX) intravenously at a dose of 25 mg/kg b.w. in combination with 5 mg trimethoprim (TMP) per kg body weight. The pharmacokinetic parameters of the sulfonamides as well as their main metabolites (acetyl sulfonamides) were not significantly different in healthy and febrile pigs. In healthy and pneumonic pigs, the mean elimination half-lives of SDM were 12.9 h and 13.4 h, respectively, those of SMX 2.5 h and 2.7 h, respectively, and those of TMP 2.8 h and 2.6 h, respectively. Distribution volumes in healthy and febrile pigs of SDM and SMX varied between 0.2 and 0.4 L/kg, and those of TMP between 1.1 and 1.6 L/kg. The mean AUC of TMP was decreased and the volume of distribution and total body clearance of TMP were increased in febrile pigs. Protein binding of the drugs and metabolites studied were not significantly changed after toxin-induced fever. The extent of protein binding of SDM, SMX and TMP was in the range 94–99%, 45–56% and 40–50%, respectively. Based on knowledge of in vitro antimicrobial activity of the drug combinations against A.pleuropneumoniae it was concluded that after intravenous administration of the dose administered (30 mg/kg of the combination preparations) to healthy and pneumonic pigs, plasma concentrations of SMX and TMP were above the concentration required for growth inhibition of 50% of A., pleuropneumoniae strains for approximately 16 h, whereas bacteriostatic plasma concentrations of SDM were still present after TMP had been eliminated from plasma. Because of similar elimination half-lives of SMX and TMP in pigs this combination is preferred to the combination of SDM with TMP.  相似文献   

4.
Trimethoprim/sulfonamide combinations in the horse: a review   总被引：1，自引：0，他引：1  
Van Duijkeren, E., Vulto, A.G., van Miert, A.S.J.P.A.M. Trimethoprim/sulfonamide combinations in the horse: a review. J. vet. Pharmacol. Therap. 17 , 64–73. The indications for use, side-effects, and pharmacokinetic parameters of trimethoprim, sulfonamides and their combinations in the horse are reviewed. Trimethoprim/sulfonamide (TMPS) combinations are used for the treatment of various diseases caused by gram-positive and gram-negative bacteria, including infections of the respiratory tract, urogenital tract, alimentary tract, skin Joints and wounds- TMPS combinations can be administered orally, since absorption from the gastrointestinal tract is relatively good. However, peak serum concentrations can vary significantly between individual horses. Feed intake affects serum concentrations after oral administration. Concentrations of non-bound trimethoprim (TMP) and sulfadiazine (SDZ) in synovial fluid and peritoneal fluid are equal to serum concentrations after intravenous (i.v.) administration, and high concentrations are found in urine. Concentrations of TMP and sulfamethoxazole (SMX) in cerebrospinal fluid after i.v. administration exceed the minimum inhibitory concentration for common equine pathogens. The volume of distribution is 1.5-2.71/kg for TMP and 0.3-0.7 1/kg for various sulfonamides. The plasma half-life of TMP is 1.9-4.3 h, whereas the plasma half-lives of the different sulfonamides vary between 2.7 and 14.0 h. About 50% of total TMP is bound to plasma proteins. The binding of sulfadox-ine to plasma proteins depends on total plasma concentration and varies between 14% and 72%. The binding of other sulfonamides to plasma proteins may range from 33% for sulfaphenazole (SPZ) to 93% for sulfadimethoxine (SDM). Sulfonamides are metabolized by acetylation of the para-amino (N4) group and by hydroxylation of the methyl group and the pyrimidine ring. The metabolic pathways of TMP in the horse are not fully known. Bacterial resistance to TMPS combinations is still relatively low. The sensitivity of different micro-organisms may vary with the relative activity of the sulfonamide used in the combination. The advised oral and i.v. dose rate is 15–30 mg/kg (in a 1:5 TMP/S ratio) with a dose interval of 12 h. The acute toxicity of TMPS is low, but there have been several reports of death after i.v. administration, probably due to vagal stimulation and subsequent bradycardia and vasodilatation caused by the pharmaceutical formulation (excipients, solvents) used. Future research should concentrate on establishing the optimum pyrimidine/sulfonamide combination and its dosing regimen for antimicrobial therapy in horses.  相似文献   

5.
Metabolites of Monascus ruber in silages   总被引：2，自引：0，他引：2  
A total of 233 silages were examined and found that Monascus ruber was present in 43 samples with counts between 1 × 103 and 9 × 106 colony-forming units (CFU)/g (mean: 2 × 105 CFU/g). Monacolin KL and the hydroxy acid monacolin KA were detected by liquid chromatography-mass spectrometry in 45 and 50 of 233 samples at levels ranging from 25–15 600 and 28–65 400  μ g/kg, respectively. Citrinin was found with high-performance liquid chromatography-fluorescence detection (FLD) in 14 (6%) samples, the concentrations varied between 2.4 and 64.2  μ g/kg. The concentrations of citrinin were low and toxic effects are not anticipated. Monacolin KA and monacolin KL occur frequently and in considerable amounts in silages. These metabolites are believed to influence the metabolic activity of rumen anaerobic fungi resulting in a poorer digestion of crude fibre.  相似文献   

6.
The prophylactic effect of in-feed medication of conventional pigs with sulphadimethoxine (SDM), sulphamethoxazole (SMX), and trimethoprim (TMP) was tested by using an Actinobacillus pleuropneumoniae infection model. In each of five experiments, six pigs were given medicated feed twice daily and three pigs received antibiotic-free feed and served as positive (unmedicated, infected) controls. The following drugs or drug combinations were tested (in mg per kg feed): 500 SDM + 100 TMP, 500 SMX + 100 TMP, 125 SMX + 25 TMP, 125 SMX (alone) and 25 TMP (alone). After six days of feed medication, all animals were endobronchially inoculated with A. pleuropneumoniae in a dose of 1-3.10(4) colony-forming units (CFU). The response to the challenge in all control pigs was characterized by fever, lethargy, anorexia, reduced water consumption, and laboured breathing. At autopsy all controls manifested a fibrinous haemorrhagic pleuropneumonia. In-feed medication with 500 SDM + 100 TMP, 500 SMX + 100 TMP as well as 125 SMX + 25 TMP resulted in an effective protection against the challenge in all treated animals. After consumption of feed medicated with 125 mg per kg SMX or 25 mg per kg TMP, pleuropneumonia was evident in all challenged pigs. The results of this study indicate an in vivo potentiation of SMX and TMP in pigs against this respiratory tract pathogen.  相似文献   

7.
Plasma disposition, metabolism, protein binding and renal clearance of sulphamethoxazole (SMZ) and trimethoprim (TMP) were studied in four pigs after intravenous administration at a dose of 40 and 8 mg/kg, respectively. SMZ and TMP were quickly eliminated (mean elimination half-lives: 2.7 and 2.4 h, respectively). SMZ was predominantly acetylated; no hydroxy and glucuronide derivates could be detected in plasma and urine. TMP was 0-demethylated into 4-hydroxytrimethoprim (M1) and 3-hydroxytrimethoprim (M4) metabolite and subsequently extensively glucuronidated. SMZ, TMP and its M1 metabolite were excreted predominantly by glomerular filtration, while N4-acetylsulphamethoxazole and glucuronide conjugates of the M1 and M4 metabolites of TMP were actively eliminated by tubular secretion. The proportional drug percentage being present in the urine as parent compound was 13.1% for TMP and 16.0% for SMZ. The glucuronide conjugates of the M1 and M4 metabolites formed the main part (81.5%) of urinary TMP excretion pattern.  相似文献   

8.
Three once-daily oral doses of 0.2 mg/kg [14C]dirlotapide were administered to beagle dogs to study the absorption, distribution, metabolism, and excretion of dirlotapide. Mean 14C recovered at 2.5 and 4.5 h after the last dose was 90%. Mean 14C in urine, bile, and feces was <1%, 1.7%, and 56% of the dose, respectively. In tissues, 26% of the 14C dose was present in the gastrointestinal tract, 6.0% in liver, and <1% each in kidney, gall bladder, heart, and brain. To further characterize drug disposition, a single 2.5-mg/kg oral dose of [14C]dirlotapide was administered to beagle dogs. More than 84% of the dose had been eliminated by 72 h in feces, with 21% of the dose present in feces as parent dirlotapide. Less than 1% of the dose was excreted in urine. In bile collected during the first 24-h postdose from three dogs, 32% and 11% of the 14C dose was present in samples from male and female dogs, respectively. Based upon metabolite profiling of plasma, excreta, and bile samples, dirlotapide was extensively metabolized to more than 20 metabolites. Biliary/fecal excretion and the potential for enterohepatic recycling of metabolites are suggested.  相似文献   

9.
The pharmacokinetics and bioavailability of trimethoprim-sulfamethoxazole (TMP-SMX) were studied in six healthy male-castrate alpacas (Lama pacos) after intravenous (i.v.) or oral (p.o.) drug administration of 15 mg/kg TMP-SMX using a crossover design with a 2-week washout period. After 90 days one group (n = 3) was given a p.o. dose of 30 mg/kg TMP-SMX and the other group (n = 3) was given a p.o. dose of 60 mg/kg TMP-SMX. After i.v. administration of 15 mg/kg of TMP-SMX the mean initial plasma concentration (C0) was 10.75 +/- 2.12 microg/mL for trimethoprim (TMP) and 158.3 +/- 189.3 microg/mL for sulfamethoxazole (SMX). Elimination half-lives were 0.74 +/- 0.1 h for TMP and 2.2 +/- 0.6 h for SMX. The mean residence times were 1.45 +/- 0.72 h for TMP and 2.8 +/- 0.6 h for SMX. The areas under the respective concentration vs. time curves (AUC) were 2.49 +/- 1.62 microg h/mL for TMP and 124 +/- 60 microg h/mL for SMX. Total clearance (Clt) for TMP was 21.63 +/- 9.85 and 1.90 +/- 0.77 mL/min kg for SMX. The volume of distribution at steady state was 2.32 +/- 1.15 L/kg for TMP and 0.35 +/- 0.09 L/kg for SMX. After intragastric administration of 15, 30 and 60 mg/kg the peak concentration (Cmax) of SMX were 1.9 +/- 0.8, 2.6 +/- 0.4 and 2.8 +/- 0.7 microg/mL, respectively. The AUC was 9.1 +/- 5, 25.9 +/- 3.3 and 39.1 +/- 4.1 microg h/mL, respectively. Based upon these AUC values and correcting for dose, the respective bioavailabilities were 7.7, 10.5 and 7.94%. Trimethoprim was not detected in plasma after intragastric administration. These data demonstrate that therapeutic concentrations of TMP-SMX are not achieved after p.o. administration to alpacas.  相似文献   

10.
The effect of the endocrine-disrupting chemical 3,3',4,4',5-pentachlorobiphyenl (PCB 126) on intestinal microbiota after oral administration, and the improvement of intestinal microbiota and feces quantity by the subsequent administration of Lactobacillus acidophilus or Lactobacillus reuteri was investigated. All the rats were given 100 μg/kg bodyweight of PCB 126. The changes in bacterial counts were confirmed using a culture method. The administration of PCB 126 tended to decrease the bacterial counts of lactobacilli (109.6−1010.2 to 108.8−109.2) and bifidobacteria (105.3−106.1 to 103.6−104.2), and to increase those of Enterobacteriaceae (108.2−109.1 to 109.4−1010.3) and staphylococci (106.6−107.4 to 107.2−108.4) compared to no PCB 126 administration. After administration of PCB 126, L. acidophilus or L. reuteri orally administered to rats caused Enterobacteriaceae and staphylococci counts to decrease, suggesting that the intestinal microbiota was improved by the lactobacilli. The administration of L. acidophilus and L. reuteri improved the balance of intestinal microbiota, and defecation volume returned to its normal level. L. acidophilus and L. reuteri have a remedial effect on intestinal microbiota affected by PCB 126 and can function to lessen accumulated PCB 126 volume.  相似文献   

11.
van't Klooster, G.A.E., Blaauboer, B.J., Noordhoek, J. & van Miert, A.S.J.P.A.M. Sulfadimidine metabolism in vitro: II. comparative studies in cultured rat, goat, sheep and cattle hepatocytes. J. vet. Pharmacol. Therap. 16, 454–461.
Hydroxylation and acetylation of sulphadimidine (SDD) and the deacetylation of N4-acetyl SDD was investigated in cultured hepatocytes from male and female rats, from male and female goats and from female sheep and cattle. Significant sex differences were observed for hydroxylation of SDD in hepatocytes from rat and goat. In goat, sheep and cow hepatocytes, the hydroxylation pathway is relatively important, whereas in rat hepatocytes, acetylation is predominant. Hepatocytes of all four species deacetylated N4-acetyl SDD. In ruminant hepatocytes, deacetylating activity was of considerable importance, whereas in rat hepatocytes, it appeared a minor pathway of metabolism. Similar to the in vivo situation, formation of N4-acetyl SDD in cultured hepatocytes results from an equilibrium of acetylation and deacetylation. A good correlation was found between results in isolated hepatocytes and previous findings in vivo , both in levels of species-related activities and in acetylation-hydroxylation ratios. In conclusion, cultured hepatocytes appear a useful in vitro model to study comparative sulfonamide metabolism.  相似文献   

12.
Fenbendazole (FBZ) was administered intraruminally at 5.0 mg/kg, containing a trace of [14C]-FBZ, to sheep fitted with a permanent bile duct cannula and the behaviour of FBZ and its metabolites examined in bile and plasma. Of the administered radiolabeled dose, 47% was secreted in bile of which 34% was accounted for as conjugated and 4% as unconjugated (free) metabolites. Hydroxylated oxfendazole (OH.OFZ) was the major biliary metabolite contributing 66%, and hydroxy-FBZ (OH.FBZ) 27%, of the total metabolites characterized. Small amounts of OFZ and hydroxy FBZ sulphone (OH. FBZ.SO2) were also present in bile. The rapid appearance of OH.OFZ in bile, even before maximum concentrations of OFZ occurred in plasma, indicated that sulphoxidation and hydroxylation was the major route of FBZ metabolism.
Following intraduodenal infusion of free biliary metabolites, FBZ and its metabolites rapidly appeared in bile indicating absorption from the small intestine. When conjugated metabolites were infused they continued to appear in bile for a further 15–20 h after cessation of infusion indicating that absorption of hydroxylated metabolites occurred largely after bacterial deconjugation in the large intestine. Approximately 40% of biliary metabolites were estimated to undergo enterohepatic reabsorption but they contributed minimally to the metabolite content in plasma. It is suggested that during the process of recycling, biliary metabolites make substantial contact with parasites in the mucosa of the small and large intestine thereby contributing to the anthelmintic activity of FBZ.  相似文献   

13.
Plasma disposition of aditoprim, a new dihydrofolate reductase inhibitor, was studied in healthy cows and cows with endotoxin-induced mastitis. A single dose of 5 mg of aditoprim/kg of body weight was administered IV to 5 healthy cows and to the same cows 3 weeks later at 2 hours after intramammary infusion of 0.1 mg of endotoxin into the rear quarters. Mastitis developed in all endotoxin-infused quarters and cows had systemic signs of disease (fever, tachycardia, depression) from 2 to 10 hours after infusion of endotoxin. Pharmacokinetic characteristics of aditoprim in healthy cows were a large volume of distribution (6.28 L/kg), a systemic clearance of 0.82 L/h/kg, and an elimination half-life of 7.26 hours. In cows with mastitis, plasma concentrations of aditoprim were lower between 5 and 26 hours after injection. The systemic clearance (1.00 L/h/kg) and the volume of distribution (12.25 L/kg) were significantly higher in cows with mastitis, but elimination half-life was not significantly different. The lower plasma concentrations of aditoprim between 5 and 26 hours after injection in cows with mastitis are explained by fluid compartment shifts and/or blood flow changes induced by mastitis, although increased elimination of aditoprim in cows with mastitis cannot completely be ruled out. The antibacterial activity of aditoprim is nearly the same as that of trimethoprim. The longer elimination half-life time of aditoprim, however, indicates that it may have a practical pharmacotherapeutic advantage over trimethoprim.  相似文献   

14.
The pharmacokinetics and metabolic fate of labelled compounds were investigated after intramuscular administration of 3H-radiolabelled etiproston to nine cows. Elimination was rapid ( t 1/2β= 2.8 h). Forty-eight h after administration 92.6% of the radioactivity had been eliminated, mainly via the urinary (66% at 48 h) and faecal routes (26% at 48 h). In comparison, little elimination in milk occurred (less than 0.034% dose/l by 24 h). Radioactivity at the injection site 48 h after administration was seen in one cow (< 4.68 × 10-5% dose/g). No radioactivity was detected in the tissues. Urinary metabolites were purified and isolated using XAD-2 extraction and preparative HPLC in reverse and normal phases. The main urinary metabolite, identified by mass spectrometry, was the tetranor acid derivative in equilibrium with its lactone form.  相似文献   

15.
Technetium-99m hexamethylpropyleneamine oxine (99mTc-HMPAO) and Indium-111 oxine (111In-oxine) labeled canine gramulocytes were evaluated in vitro over a six hour period. Labeling efficiency for 99mTC-HMPAO and 111In-oxine labeled granulocytes was 39.6%± 8.0% and 60.6%± 17.6% (mean ± SD) respectively. The mean in vitro elution of the radiolabel ranged from 8.7-14.0% for the 99mTc-HMPAO grannulocytes and from 6.1-9.0% for the 111In-oxine granulocytes. Mean cell viability, for the 99mTc-HMPAO, 111In-oxine and non-radiolabeled control granulocytes ranged from 97.8-99.4%, 96.4-98.5% and 98.2-99.0%, respectively. The phagocytic ability of the 99mTc-HMPAO, 111In-oxine and control granulocytes ranged from 47.5-54.1%, 38.9-56.2% and 46.6-57.8% respectively over the six hour study period. Although labeling efficiency using 111In-oxine was significantly (P=0.05) better than 99mTc-HMPAO, there was no significant difference in label retention of the two radiolabels. There was no significant difference in viability or phagocytic function during the six hour study period. Considering the potential cost advantage and the superior imaging qualities of Technetium-99m relative to Indium-111, 99mTc-HMPAO appears to be a good alternative to 111In-oxine as a granulocyte label.  相似文献   

16.
Seven dogs with thyroid gland carcinoma were treated with 131I and hormone suppressive therapy either alone (3 dogs) or in combination with surgery (3 dogs) or 137Cs teletherapy and chemotherapy (1 dog). Empirically chosen doses of 75 to 137 mCi of 131I were given orally (2 dogs) and intravenously (5 dogs). Adverse effects were limited to acute, transient bone marrow hypoplasia and pancytopenia. Nominal objective reduction in tumor volume or size and number of pulmonary metastases was observed in 4 dogs treated with 131I and thyroxine. Of these 4 dogs, 2 had stable disease for periods of 4 and 12 months while a third dog had stable disease for 27 months following two 131I treatments at 3 month intervals. The fourth dog had progressive disease. Two dogs with mediastinal metastases showed reduction in localization of 99mTc pertechnetate and radioiodine following 2 and 3 treatments using 131I. It appears that relatively high doses of 131I can be used safely for the treatment of canine thyroid tumors and that further investigation can be justified to define its efficacy.  相似文献   

17.
This study presents a depletion study for sulfadiazine and trimethoprim in muscle plus skin of gilthead sea bream (Sparus aurata L.). N4‐acetyl‐sulfadiazine, the main metabolite of sulfadiazine (SDZ), was also examined. The fish were held in seawater at a temperature of 24–26 °C. SDZ and trimethoprim (TMP) were administered orally with medicated feed for five consecutive days at daily doses of 25 mg SDZ and 5 mg TMP per kg of fish body weight per day. Two different diets, fish oil‐ and plant oil‐based diets, were investigated. Ten fish were sampled at each of the days 1, 3, 5, 6, 8, 9, 10, and 12 after the start of veterinary medicine administration. However for the calculation of the withdrawal periods, sampling day 1 was set as 24 h after the last dose of the treatment. Fish samples were analyzed for SDZ, TMP, and acetyl‐sulfadiazine (AcSDZ) residues by liquid chromatography–mass spectrometry. SDZ and TMP concentrations declined rapidly from muscle plus skin. Considering a maximum residue limit of 100 μg/kg for the total of sulfonamides and 50 μg/kg for TMP residues in fish muscle plus skin, the withdrawal periods of the premix trimethoprim‐sulfadiazine 50% were calculated as 5 and 6 days, at 24–26 °C, in fish oil (FO) and plant oil (PO) groups, respectively. The investigation of this work is important to protect consumers by controlling the undesirable residues in fish.  相似文献   

18.
The kinetic disposition of orally administered [3H]-Ivermectin (IVM) was examined in sheep in which the feed intake was maintained at either 800 or 400 g/day. The [3H]-metabolites were almost completely associated with particulate digesta in the rumen. In the low feed intake group the digesta flow was slower than in sheep on high feed intake. This resulted in an extended residence time and greater availability of IVM and its metabolites. The anthelmintic efficacy of IVM was then examined in sheep in which feed intake was reduced from 800 g/day to 400g/36h prior to and 36 h after IVM administration. In sheep with reduced intake 97% of IVM-resistant Haemonchus contortus were removed, compared with 53% in sheep maintained on high feed intake.  相似文献   

19.
The clearance of inulin and creatinine were almost identical in horses, indicating that creatinine clearance can be used for estimation of the glomerular filtration rate in horses. Trimethoprim (TMP) is excreted in urine by glomerular filtration, active tubular secretion and back-diffusion. The clearance of TMP is highly influenced by urine pH, but also by the plasma concentration of the drug and by the degree of diuresis. The results indicate self-depression of the active tubular secretion of TMP at plasma concentrations above 1–2 μg/ml. The renal excretion of sulphadoxine in horses involves glomerular filtration and a pronounced back-diffusion. The clearance of sulphadoxine is dependent on urine pH and increases with increasing pH. The clearance of N4-acetyl sulphadoxine was higher than the clearance of the parent compound. The renal excretion of N4-acetyl sulphadoxine was shown to involve glomerular filtration, active tubular secretion and back-diffusion.  相似文献   

20.
Reliabilities for genomic estimated breeding values (GEBV) were investigated by simulation for a typical dairy cattle breeding setting. Scenarios were simulated with different heritabilites ( h 2) and for different haplotype sizes, and seven generations with only genotypes were generated to investigate reliability of GEBV over time. A genome with 5000 single nucleotide polymorphisms (SNP) at distances of 0.1 cM and 50 quantitative trait loci (QTL) was simulated, and a Bayesian variable selection model was implemented to predict GEBV. Highest reliabilities were obtained for 10 SNP haplotypes. At optimal haplotype size, reliabilities in generation 1 without phenotypes ranged from 0.80 for h 2 = 0.02 to 0.93 for h 2 = 0.30, and in the seventh generation without phenotypes ranged from 0.69 for h 2 = 0.02 to 0.86 for h 2 = 0.30. Reliabilities of GEBV were found sufficiently high to implement dairy selection schemes without progeny testing in which case a data time-lag of two to three generations may be present. Reliabilities were also relatively high for low heritable traits, implying that genomic selection could be especially beneficial to improve the selection on, e.g. health and fertility.  相似文献   

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