Mammary and renal excretion of sulphadoxine and trimethoprim in cows

DAVITIYANANDA, DANIS and FOLKE RASMUSSEN: Mammary and renal excretion of sulphadoxine and trimethoprim in cows. Acta vet. scand. 1974, 15, 340–355. — In 21 experiments on 5 healthy, nonpregnant cows are sulphadoxine and trimethoprim infused intravenously for maintenance of constant levels of the drugs through the experimental periods. The experiments show that both sulphadoxine and trimethoprim are bound to the proteins in blood plasma and milk. Further it is demonstrated that sulphadoxine (an acid) is excreted into milk in concentrations lower than in blood plasma while trimethoprim (a base) is excreted into milk in concentrations higher than in blood plasma. Both results are consistent with the theory that drugs are excreted through the mammary gland by passive diffusion.Glomerular filtration and back-diffusion are both involved in the renal handling of sulphadoxine and trimethoprim. For trimethoprim active tubular secretion is also demonstrated. Both the mammary and renal handling of sulphadoxine as well as trimethoprim are influenced by the pH of milk and urine, respectively. The experiments underline that it is the unionized, non-protein-bound fraction of the drugs which diffuses through biological membranes.sulphadoxine; trimethoprim; mammary excretion; renal excretion; cow.     

Plasma and milk kinetic of eprinomectin and moxidectin in lactating water buffaloes (Bubalus bubalis)

The pharmacokinetics and mammary excretion of moxidectin and eprinomectin were determined in water buffaloes (Bubalus bubalis) following topical administration of 0.5mgkg(-1). Following administration of moxidectin, plasma and milk concentrations of moxidectin increased to reach maximal concentrations (C(max)) of 5.46+/-3.50 and 23.76+/-16.63ngml(-1) at T(max) of 1.20+/-0.33 and 1.87+/-0.77 days in plasma and milk, respectively. The mean residence time (MRT) were similar for plasma and milk (5.27+/-0.45 and 5.87+/-0.80 days, respectively). The AUC value was 5-fold higher in milk (109.68+/-65.01ngdayml(-1)) than in plasma (23.66+/-12.26ngdayml(-1)). The ratio of AUC milk/plasma for moxidectin was 5.04+/-2.13. The moxidectin systemic availability (expressed as plasma AUC values) obtained in buffaloes was in the same range than those reported in cattle. The faster absorption and elimination processes of moxidectin were probably due to a lower storage in fat associated with the fact that animals were in lactation. Nevertheless, due to its high excretion in milk and its high detected maximum concentration in milk which is equivalent or higher to the Maximal Residue Level value (MRL) (40ngml(-1)), its use should be prohibited in lactating buffaloes. Concerning eprinomectin, the C(max) were of 2.74+/-0.89 and 3.40+/-1.68ngml(-1) at T(max) of 1.44+/-0.20 and 1.33+/-0.0.41 days in plasma and milk, respectively. The MRT and the AUC were similar for plasma (3.17+/-0.41 days and 11.43+/-4.01ngdayml(-1)) and milk (2.70+/-0.44 days and 8.49+/-3.33ngdayml(-1)). The ratio of AUC milk/plasma for eprinomectin was 0.76+/-0.16. The AUC value is 20 times lower than that reported in dairy cattle. The very low extent of mammary excretion and the milk levels reported lower than the MRL (20ngml(-1)) supports the permitted use of eprinomectin in lactating water buffaloes.     

Mammary and renal excretion of chlorpromazine in goats

In experiments on goats it was found that the binding of chlorpromazine (Cpz) to the proteins in plasma and milk ranged between 91–99 and 91–97 %, respectively, and was independent of the drug concentration in the samples. The in vitro binding of chlorpromazine in whole milk (96%) was significantly higher (P<0.01) than the protein binding in skim milk (91%) because the drug was concentrated in the butterfat. The concentration of Cpz was always higher in the milk than in the corresponding plasma samples. The renal clearance of Cpz in goats with normal urine pH was very small (0.16 ml min^-1) due to the high degree of plasma protein binding and of back diffusion. The mechanisms involved during the renal excretion of Cpz in goats included glomerular filtration, probably active tubular secretion and pH dependent back diffusion.     

Active mammary excretion of N4-acetylated sulphanilamide

After administration of sulphanilamide to goats and cows, sulphanilamide is excreted into milk. The concentrations of sulphanilamide in ultrafiltrate of milk (M. Ultr.) and blood plasma (P. Ultr.) are equal and the ratio M. Ultr./P. Ultr. is 1.0. The pK_a of sulphanilamide is 10.4 and thus, sulphanilamide is un-ionized in both milk and blood plasma. Therefore, sulphanilamide is excreted into milk in accordance to the theory of passive diffusion of the non-protein-bound and un-ionized fraction in blood plasma (Rasmussen 1958, 1966; Miller et al. 1967). A similar ratio was expected for acetylated sulphanilamide with a pK_a of 10.3. However, the concentration of the acetylated derivative is always found higher in milk than in plasma. This might be due to formation of acetylated sulphanilamide in the mammary tissue, as demonstrated by Rasmussen & Linzell (1967) or active excretion of the compound just as in the case of N⁴-acetylated p-aminohip-puric acid (Rasmussen 1969).     

The renal clearance of inulin, creatinine, trimethoprim and sulphadoxine in horses

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.     

The effect of vitamin C supplementation on plasma concentration and urinary excretion of vitamin C in cattle

We investigated the plasma concentration and urinary excretion of vitamin C in cows supplemented with vitamin C. Five cows (mean BW = 597 kg) were allocated to a 5 x 5 Latin square design and supplemented with a vitamin C preparation coated with hydrogenated soybean oil at 0, 10, 20, 40, or 60 mg of vitamin C per kg of BW per day for 9 d. Plasma and urine samples were collected for measuring vitamin C concentration. Urinary excretion of vitamin C was expressed as the ratio of vitamin C to creatinine. Plasma vitamin C concentration and urinary vitamin C excretion increased quadratically as dietary vitamin C increased (P < 0.001); that is, the lowest dose affected neither plasma vitamin C concentration nor urinary vitamin C excretion but the plasma vitamin C concentration and urinary vitamin C excretion increased (P < 0.05) with increasing supplementation of vitamin C at greater doses. This suggests that plasma vitamin C concentration affects urinary excretion of vitamin C in cattle and that plasma vitamin C concentration exceeded the renal threshold for vitamin C in the cows receiving vitamin C at 20 mg/kg of BW per day. Furthermore, increased urinary excretion of vitamin C appears to limit plasma vitamin C concentration in response to vitamin C intake. The daily excretion of vitamin C was estimated by the reported value of daily creatinine excretion, indicating that the daily amount of vitamin C excreted into urine was more than half of supplied vitamin C. Therefore, a large part of supplied vitamin C probably escapes ruminal degradation and is absorbed but excreted into urine.     

Pharmacokinetics of eprinomectin in plasma and milk following topical administration to lactating dairy cattle

The pharmacokinetics and mammary excretion of eprinomectin were determined in cattle following topical administration at a dose rate of 0.5 mg kg(-1). The kinetics of plasma and milk concentrations were analysed using a one-compartment model. The maximum plasma concentration of 43.76 ng ml(-1)occurred 2.02 days post administration, and the mean residence time was 4.16 days. Eprinomection was detected in the milk at the first sampling time and thereafter for at least 15 days. Comparison of the milk and plasma data demonstrated the parallel disposition of the drug in the milk and plasma with a milk / plasma concentration ratio of 0. 102+/-0.048. The amount of drug recovered in the milk during this period was 0.109% +/- 0.038 of the total administered dose. This very low extent of mammary excretion resulted in low concentrations of eprinomectin in milk. This supports the permitted use in lactating cattle, as the maximum level of residue in milk did not exceed the maximum acceptable limit of 30 ng ml(-1).     

Secretory component and IgA expression by epithelial cells in sow mammary gland and mammary secretions

Secretory component (SC) and IgA expression of epithelial cells were studied in the mammary tissue and mammary secretions of sows. In mammary tissue, SC was not detected until day 105 of gestation. From the time of delivery (day 115) to the time of established lactation, the proportion of epithelial cells containing sc rose from 20 per cent to nearly 100 per cent. There was no IgA in alveolar epithelial cells until day 105 of gestation; on day 115, IgA positive epithelial cells were present in 10 per cent of the alveoli, which increased to 80 per cent during lactation. Epithelial cells represented more than 20 per cent of the total cells in colostrum, and predominated over leucocytes in milk. In colostrum, these epithelial cells (9 to 15 μm) showed weakly positive membrane, sc, contained cytoplasmic SC and had a limited capacity for in vitro proliferation. Ten per cent of epithelial cells contained intracytroplasmic IgA. In milk, the epithelial cells were larger (15 to 40 μm) with a higher expression of both membrane and intracytoplasmic sc; 66 per cent of these cells expressed intracytoplasmic IgA. These data showed that the capacity of mammary epithelium to process IgA to secretory IgA was complete at the end of mammary gland organisation, and established that the epithelial cells of milk contribute to the transfer of IgA to neonates.     

Renal excretion of digoxin in swine and goats.

In experiments on swine and goats the renal excretion of digoxin was examined, and it was found that the renal clearance of non-protein-bound digoxin in swine was lower than creatinine clearance which expresses filtration clearance. Correlation analysis showed that the renal clearance of digoxin in swine was not significantly influenced by the concentration of non-protein-bound digoxin in plasma and the pH of the urine, while there was a significant positive correlation between the clearance and the urine flow rate (Table 4). On the other hand, the renal clearance of digoxin in goats was significantly influenced by the concentration of non-proteinbound digoxin in plasma and by urine pH (Table 4). From these results it is concluded that glomerular filtration and back-diffusion are involved in the renal handling of digoxin in both swine and goats. In addition active tubular secretion is also involved in the renal excretion of digoxin in goats.     

Assessment of acid-base status of cats with naturally occurring chronic renal failure

Metabolic acidosis is reported to be a common complication of feline chronic renal failure (CRF) but acid-base status of feline patients with this disease is rarely assessed by general practitioners. A cross-sectional study involving 59 cases of naturally occurring feline CRF was conducted to determine the prevalence of acid-base disturbances. Cases were categorised on the basis of their plasma creatinine concentrations as mild, moderate or severe. A group of 27 clinically healthy, age-matched cats was assessed for comparison. A low venous blood pH (<7.270) was found in 10 of the 19 severe cases (52.6 per cent), three of the 20 moderate cases (15 per cent) and none of the 20 mild cases. Acidaemia was associated with an increased anion gap contributed to by both low plasma bicarbonate and low chloride ion concentrations. Biochemical analysis of urine samples showed urine pH to decrease with increasing severity of renal failure. Urinary loss of bicarbonate was not associated with the occurrence of acidaemia and there was a tendency for urinary ammonium ion excretion to decrease as the severity of renal failure increased. Cats with naturally occurring CRF do not show plasma biochemical evidence of acid-base disturbances until the disease is advanced.     

Clinicopathological and ultrasonographic findings in 40 water buffaloes (Bubalus bubalis) with traumatic pericarditis

Forty buffaloes with traumatic pericarditis were examined to characterise the ultrasonographic findings in buffaloes with traumatic pericarditis, determine the extent of the lesions and assess the prognosis. The most noticeable clinical presentations were presternal oedema (73 per cent) and jugular and mammary vein distension (88 per cent). Laboratory findings included neutrophilic leucocytosis, elevated total protein concentration, hypoalbuminaemia, hypergammaglobulinaemia and increased concentration of free fatty acids. Ultrasonographically, fluid in the pericardium appeared as either mild or massive anechoic accumulations containing fibrin threads or were imaged as homogenous, echogenic pericardial effusions. Moderate to severe corrugation of the reticular wall was observed. Deposits of fibrinous tissue interspersed with fluid pockets were seen between the reticulum, dorsal ruminal sac and diaphragm. Perireticular and mediastinal abscesses were imaged and appeared as echogenic lines with anechoic, echogenic, homogenous or heterogeneous contents. Additional ultrasonographic findings included hepatomegaly, dilation of the caudal vena cava, hepatic and portal veins, ascites, echogenic pleural effusions and vegetations of the tricuspid, mitral and pulmonary valves. The ultrasonographic findings were confirmed at postmortem examination.     

Mammary uptake and excretion of prostanoids in relation to mammary blood flow and milk yield during pregnancy-lactation and somatotropin treatment in dairy goats

Mammary arterious − venous differences (A − V) and excretion into milk of four prostanoids were related to changes in milk yield and milk vein blood velocity (MBV) in goats at different stages of pregnancy and lactation, and during somatotropin (ST) treatment in mid-lactation. Arterial concentrations and mammary A − V for the vasodilators prostacyclin (PGI₂) and prostaglandin (PG) E₂ (measured as 6-keto-PGF₁ and bicyclic PGE₂, respectively) decreased from late pregnancy to lactation. A − V were negatively correlated to MBV (r = −0.32 to −0.34). Arterial concentrations of the vasoconstrictors PGF₂ and TXA₂ (measured as TXB₂) changed similarly, but no A − V across the mammary gland were found. The vasodilator to vasoconstrictor ratio in plasma was around 1:1, and in skimmed milk around 0.29–0.49 due to significantly higher TXB₂ levels in milk compared to plasma. Close linear correlations were established between milk yield and excretion of TXB₂ into milk (r = 0.80, P < 0.001), and between MBV and PGE₂ excretion into milk (r = 0.69, P < 0.001). ST treatment stimulated MBV and mammary prostanoid supply, and decreased prostanoid concentration in milk vein plasma. The high arterial levels of prostaglandins during pregnancy most likely reflected uterine synthesis. Our results support a role for PGI₂ and PGE₂ in local mammary blood flow regulation during lactation. Increased mammary uptake of these two prostanoids may be involved in the mammary blood flow response to ST. TXA₂ may be synthesized by mammary epithelial as well as vascular cells, and TXA₂ may be an important factor in regulation of mammary function.     

12月龄生长母水牛绝食代谢的研究

用传统开路式牛用呼吸面具对12月龄母水牛绝食产热(FHP)进行研究。结果表明:①12月龄母水牛FHP为334.03KJ/KgW0.75·d;每天排出内源尿氮(EUN)为31.06g;代谢体重每天排出EUN为0.53g;蛋白分解产热占总产热量为17.99%;EUN与FHP比值为1.60mg/KJ。②12月龄母水牛维持净能需要:NEm=400.84KJ/W0.75d。     

Active mammary excretion of N4-acetylated p-aminohippuric acid

Different excretion patterns were observed for p-amino- hippuric acid and its acetylated metabolite in mammary excretion experiments in goats and cows. The excretion of p-aminohippuric acid conformed to passive diffusion of the non-protein bound and un-ionized fraction (Rasmussen 1958, 1966) as described by Miller et al. (1967). Thus, the p-aminohippuric acid (pK_a 3.8) appeared in ultrafiltrates of milk in concentrations 1/4—1/10 of the concentrations in ultrafiltrates of blood plasma. The concentrations of acetylated p-aminohippuric acid (pK_a 3.9) in ultrafiltrates of milk were on the other hand equal to or higher than in ultrafiltrates of blood plasma.     

Excretion of zinc in lactating cows receiving various supply of zinc]

Studies were carried out with 5 lactating cows receiving a semisynthetic diet to trace the pattern of zinc excretion in the faeces, urine and milk under conditions of Zn depletion and repletion. Faecal Zn concentrations were found to be drastically reduced during a 6-week period of Zn depletion. The Zn supply to the animals at different levels of Zn repletion (varying between 22 mg and 436 mg Zn per kg) was well reflected in the corresponding faecal Zn concentrations. Similarly, faecal Zn excretion expressed as the percentage of Zn supplied with the diet was shown to change with the level of Zn supply. In the range between 6 mg and 54 m Zn per kg of dietary dry matter the level of relative faecal Zn excretion increased from 42% to 56% whereas with higher Zn supplements (up to 436 mg/kg) only slight increases (up to 60%) were observed. This indicates that the organism exhibits a strong tendency to maintain a physiological balance; this tendency is all the more pronounced with increasing Zn depletion; thus after 19 weeks of Zn depletion as little as 25% of the administered amount of Zn was excreted in the faeces. The average minimum of urinary Zn concentrations was 0.25 mg Zn per litre. The Zn concentrations in urine were not found to be dependent on the Zn supply. The level of relative Zn excretion in the milk was markedly increased despite the reduced concentrations of milk Zn during the periods of Zn deficiency. At the beginning of Zn depletion rather more zinc was released with the milk than was taken up with the Zn deficient diet. The mean proportion of milk Zn in the total amount of dietary Zn over the 6-week depletion period was 91%. With Zn amounts of 22 mg, 54 mg, 87 mg, 108 mg, 130 mg and 436 mg per kg of diet 23.7%, 13.1%, 12.9%, 5.7%, 4.3%, and 1.7% of the dietary Zn were excreted with the milk. Thus, a relative decrease of Zn excretion in the milk was observed, i.e. relative to the level of Zn supplementation.     

Excretion of A Single Dose of Selenium in Sheep

The excretion of Se⁷⁵ via the feces and urine was studied in 30 sheep. Se⁷⁵-sodium selenite was injected subcutaneously, using three different doses ranging from a tracer dose to a therapeutic dose. By the intraruminal route the substance was given in a tracer dose and a therapeutic dose. Se⁷⁵-selenomethionine was injected subcutaneously and intraruminally in a tracer dose. Se⁷⁵-selenocystine was given intravenously in a dose higher than that regarded as a therapeutic dose.After intraruminal injection a higher percentage of the dose was excreted via the feces than via the urine. After the two highest subcutaneous doses the urinary excretion was significantly higher than the fecal excretion. After a high selenium dose the percentage eliminated via the urine was greater than after a low dose, whether the subcutaneous or the intraruminal route was used.The fecal and urinary excretion of Se⁷⁵ was of approximately the same order after injection of Se⁷⁵-selenomethionine and Se⁷⁵-selenocystine as after injection of the tracer dose of Se⁷⁵-sodium selenite.In 2 sheep, 1.4 per cent and 3.7 per cent, respectively, of a therapeutic dose were excreted via the bile in 48 hours.Less than 3 per cent of a subcutaneous dose was eliminated with the expired air in 24 hours.Exactly how much of a therapeutic dose is excreted within, for instance, 2 weeks is difficult to establish, as the treated animal’s selenium supply with the feed is not known. In the experiments reported here, however, approximately 64 per cent of a subcutaneous and 75 per cent of an intraruminal therapeutic dose were excreted over a two-week period.     

Progesterone and pregnancy status of buffaloes treated with a GNRH agonist

The primary aim of the present study was to establish whether the treatment with a GnRH agonist on Day 5 after AI may result in the formation of an accessory corpus luteum, greater progesterone secretion, and the increased likelihood of pregnancy success in buffaloes. The study was conducted during a period of increasing daylight length when progesterone secretion is suppressed and embryonic mortality is relatively high in buffaloes. In Experiment 1, treatment with a GnRH agonist (buserelin, 12 μg) on Day 5 after AI induced acute increases in circulating concentrations of LH, FSH and oestradiol-17β. Pregnant buffaloes (n = 14) at Day 40 following AI showed an increase (P < 0.01) in milk whey progesterone concentration between Day 5 (310 ± 55 pg/ml) and Day 15 (424 ± 50 pg/ml). The non-pregnant buffaloes (n = 7) showed a decrease (P < 0.01) in progesterone level from Day 5 (410 ± 87 pg/ml) to Day 15 (188 ± 30 pg/ml) following AI. In Experiment 2, the treatment with buserelin (12 μg) on Day 5 after AI induced ovulation in 62% of the buffaloes (31/50) and these buffaloes showed a progressive increase in milk whey progesterone concentration on Day 10, 15 and 20 of pregnancy. Buffaloes that did not ovulate, recorded a relatively constant milk whey progesterone level from Day 10 to Day 20 following AI. Milk whey progesterone concentrations increased after the administration of the GnRH agonist in 97% of the pregnant buffaloes and 68% of the non-pregnant buffaloes. The diameter of the largest follicle in buffaloes that ovulated (ovulated n = 31) (8.9 ± 0.04 mm; range 4.2 – 13.0 mm) did not differ significantly from the diameter of the largest follicle in buffaloes that did not ovulate (not ovulate n = 19) (8.7 ± 0.04 mm; range: 4.0 – 12.0 mm). The latter observation suggested that notional ovulatory size follicles in buffaloes are heterogeneous with respect to stage of follicle maturation and capacity to respond to plasma LH. The present study showed that treatment with a GnRH agonist on Day 5 following AI provides a strategy to increase progesterone secretion and the likelihood of pregnancy in buffaloes mated during periods of increasing daylight length.     

A simple, rapid method for differential cell counts in porcine mammary secretions.

The use of the fluorescent dye acridine orange for making differential cell counts in mammary secretions from sows was investigated, and the variations in cell type during the lactation period were also studied. In untreated samples of mammary secretions polymorphonuclear leucocytes, mononuclear phagocytes, lymphocytes and epithelial cells could be identified with certainty, and the methodological error was small (1.80 to 2.22 per cent). The mammary secretions could be stored at 4 degrees C for six hours without any effect on the differential count. Washing the secretions decreased the percentage of polymorphonuclear leucocytes and increased the percentage of epithelial cells. The polymorphonuclear leucocytes predominated in colostrum (58.0 to 65.5 per cent) and epithelial cells predominated in milk (60 to 89 per cent). Polymorphonuclear leucocytes were the predominant phagocytes in all mammary secretions (7.6 to 65.5 per cent).     

Mammary secretion of oestrogens in the cow

Two experiments in vivo and one experiment in vitro were conduced to examine the mechanisms involved, which lead to mammary secretion of oestrogens and its importance for milk production and udder health in cows. In experiment 1 in six cows of the White-Black breed on day 268 of pregnancy catheters were inserted into uterine vein of pregnant horn, the abdominal aorta and the caudal superficial epigastric (milk) vein. Blood samples for estimation of oestrone, oestrone sulphate, oestradiol-17alpha and -17beta by RIA were obtained daily from day 7 pre-partum until day 1 post-partum. Only the concentration of oestradiol-17beta was statistically higher (P< or =0.01) in mammary venous plasma than in aortal and uterine plasma. In experiment 2 forty late-pregnant cows were divided into two groups according to their milk production in the previous lactation: group 1 (n=20) high-yielding cows (>6500kg milk per lactation), and group 2 (n=20) low-yielding cows (<3700kg milk per lactation). Blood samples for measurement of oestradiol-17beta by RIA were collected from milk and tail veins every fourth day during a period from day 20 prior to parturition to day 4 post-partum. The concentration of oestradiol-17beta was significantly higher (P< or =0.01) in the milk vein than in the peripheral plasma from day 12 pre-partum to parturition. In high-yielding cows the level of oestradiol-17beta in mammary venous blood was significantly higher (P< or =0.01) than in low-yielding cows. In six cows with pathological udder oedema ante-partum the concentration of oestradiol-17beta in milk vein was significantly higher (P< or =0.05) than in control cows. There were no statistically significant differences in the levels of oestradiol-17beta in cows with clinical mastitis (n=10) during 2 weeks after parturition and without it (P> or =0.05). In an in vitro experiment, homogenates of mammary tissue collected on day 7 pre-partum from two cows were incubated with 3H-androstendione. After incubation the samples were extracted and 3H-oestradiol-17beta was separated by HPLC. 3H-oestradiol-17beta was formed in a total yield of 37%. These results indicate that oestrone, oestrone sulphate and oestradiol-17alpha are not secreted by bovine mammary gland. Furthermore, the secretion of oestradiol-17beta starts about day 12 pre-partum and is associated with milk yield and udder oedema. Preliminary in vitro study suggests the synthesis of oestradiol-17beta by mammary tissue.     

Effects of exogenous urea infusion on glucose metabolism in acute heat stressed swamp buffaloes (Bubalus bubalis)

The effects of intravenous urea infusion on glucose turnover, glucose carbon recycling, glucose pool size and glucose clearance were studied in buffaloes kept in either normal ambient temperature or acute heat exposure. Heat stressed animals showed increases in glucose turnover rate, plasma glucose concentration and glucose clearance but decreased glucose carbon recycling. A marked reduction of glucose turnover and glucose clearance associated with increased plasma glucose concentration in heat stressed animals after urea infusion reflects under-utilization of this compound. Mechanisms involved in glucose metabolism during urea infusion in buffaloes are discussed.