Comparison of the pharmacokinetics and local tolerance of three injectable oxytetracycline formulations in pigs

The pharmacokinetic properties and local tolerance of three oxytetracycline formulations, one conventional (Engemycine, 10%) and two long-acting (Oxyter LA, 20% and Terramycin LA, 20%) were compared in clinically healthy cross-bred pigs following intramuscular injection of single doses (20 mg/kg body weight) in the neck region. Non-compartmental methods were used to calculate the pharmacokinetic parameters. Assessment of local tolerance was based on serum creatine phosphokinase (CPK) concentration and a combination of echographical, macroscopic and histological examinations of the intramuscular injection site. Statistically significant differences (one-way analysis of variance, F-test) were obtained between the three formulations in peak plasma concentration, peak time and mean residence time. Area under the curve did not differ significantly between the formulations. Using the Students t-test for paired data, the two long-acting formulations differed significantly in peak plasma concentration and peak time. Both of the long-acting formulations differed significantly from the conventional formulation in the peak time and mean residence time. All three formulations produced an increase in serum CPK concentrations. The increase in CPK concentration was present from 6 to 24 h post treatment for Terramycin LA, from 6 to 72 h for Oxyter LA and from 6 to 96 h for Engemycine (the conventional formulation). Echographical examination of the injection site showed lesions of an inflammatory type up to 96 h after IM injection of the drug products, whereas from 7 days the lesions represented primarily scar formation. Histological examination of tissue from the injection site did not correlate with echographical scores. The results obtained in this study show that the long-acting formulations provide significantly longer mean residence times of oxytetracycline than the conventional formulation, and that local tolerance at the IM injection site was similar for all three formulations under the experimental conditions used in this study. It can be concluded that the longacting formulations provide the advantage of a longer dosage interval when administered to pigs by intramuscular injection in the neck region at a dose of 20 mg/kg body weight.     

Serum and tissue concentrations of erythromycin in calves with induced pneumonic pasteurellosis

The effects of pneumonia on the pharmacokinetics of erythromycin administered IM and the tissue concentration changes with time were evaluated in 2-month-old calves. Pneumonia was induced by injection of Pasteurella haemolytica cultures through the thoracic wall into each lung. Six days prior to induction of pneumonia, erythromycin (15 mg/kg) was administered in a single IM dose. Erythromycin was administered again 48, 72, and 96 hours after injection of P haemolytica. On the third day of erythromycin administration (96 hours), the calves were serially euthanatized in groups of 4 calves each at 2, 5, 8, 12, 18, and 24 hours after the final dose was given. Tissue concentrations of erythromycin in kidney, liver, lung, muscle, CSF, and serum were determined. Neither the serum concentrations nor the overall pharmacokinetic values were significantly (P less than or equal to 0.05) changed by pneumonia. The concentrations of erythromycin were maximal at 5 hours for liver, muscle, and serum and at 8 hours for CSF, kidney, and lung. Serum and muscle concentrations were similar, whereas concentrations in CSF were lower than in serum and higher in kidney, liver, and lung. The lung/serum ratios were approximately 2.5 to 3 at 8 through 24 hours after IM administration. The peak concentration in lung was approximately 6 micrograms/g at 8 hours.     

拍翅运动诱发肉鸡胸深肌病的血清肌酸磷酸激酶（CPK）水平的变化

强迫ＡＡ肉鸡拍翅运动诱发胸深肌病并测定了诱发过程中试验鸡和对照鸡的血清肌酸磷酸激酶（ＣＰＫ）水平的变化。试验组鸡５天中共拍翅７次，有４／９例发生典型胸深肌病。病变特征为带有绿色坏死区的坏死性肌炎。对照组鸡不拍翅，不发生胸肌坏死。血清ＣＰＫ水平测定表明，试验组ＣＰＫ水平在拍翅后２４小时升高并维持四天，直到实验结束，与对照组保持极显著差异，说明ＣＰＫ是鸡运动应激有实用意义的血清酶指标，测定时间宜在运动后２４小时进行，与猪应激后的情况相似。在试验组内，ＣＰＫ水平仅在０—２天，０—３天，１—２天，１—３天对比组合之间有极显著差异，进一步说明运动应激后２４小时，４８小时之内为测定ＣＰＫ的可选择时间。但发病鸡与不发病鸡的ＣＰＫ水平无显著差异，说明ＣＰＫ水平虽能指示运动应激，却不能揭示胸肌病的发生，对其原因作了简要讨论。     

Colostral transfer of gamma glutamyl transferase in lambs

Serum gamma glutamyl transferase (GGT) levels in blood samples taken from normal lambs which had suckled colostrum were found to be up to 140 times normal adult levels. These high serum levels declined rapidly reaching a stable level approximately 60% higher than normal adult values by 24 days of age. Newborn lambs which had not yet consumed colostrum had GGT levels which would be considered normal in adult sheep. The GGT concentration in ewes' colostrum was up to 470 times normal serum levels. There was a significant positive correlation between serum GGT and gamma globulin levels in blood samples taken from lambs within 24 hours of birth. Lambs' serum alkaline phosphatase (AP) and serum glutamate oxaloacetate transaminase (SGOT) levels also rose concurrently with the absorption of colostral gamma globulin, with the day 1 AP values being significantly correlated with the serum gamma globulin levels. Serum AP levels declined gradually but were still well above normal adult levels at 45 days of age while SGOT levels returned to normal adult levels by two to three days after birth. It is concluded therefore that, as previously shown in calves, lambs acquire high levels of serum GGT activity from their mothers' colostrum in proportion to the amount of gamma globulin absorbed and also show a concurrent rise in serum AP activity. However the rise in SGOT levels at this time has not been observed in calves.     

Serum pharmacokinetics of oxytetracycline in sheep and calves and tissue residues in sheep following a single intramuscular injection of a long-acting preparation

The pharmacokinetics of a long‐acting oxytetracycline (OTC) formulation (Liquamycin® LA‐200®) injected intramuscularly (i.m.) at a dose of 20 mg/kg were determined in four calves and 24 sheep to determine if the approved label dose for cattle provided a similar serum time/concentration profile in sheep. The AUC for the calves was 168±14.6 (μg ? h/mL) and was significantly less than the AUC for sheep (209±43 μg ? h/mL). Using the standard two‐stage approach and a one‐compartment model, the mean Cmax for the calves was 5.2±0.8 μg/mL, and for the sheep was 6.1±1.3 μg/mL. The mean terminal phase rate constants were 0.031 and 0.033 h, and the Vdss were 3.3 and 3.08 L/kg for the calves and sheep respectively. Analysis of the data using the standard two‐stage approach, the naive pooled‐data approach and a population model gave very similar results for both the cattle and sheep data. Sheep tissue residues of OTC in serum, liver, kidney, fat, muscle and injection site were measured at 1, 2, 3, 5, 7 and 14 days after a single i.m. injection of 20 mg/kg OTC. Half‐lives of OTC residues in the tissues were 38.6, 33.4, 28.6, 25.4, 21.3, and 19.9 h for injection site, kidney, muscle, liver, mesenteric fat and renal fat, respectively. The ratio of tissue to serum concentration was fairly consistent at all slaughter times, except for the fat and injection sites. The mean ratios were 1.72, 4.19, 0.11, 0.061, 0.84 and 827 for the liver, kidney, renal fat, mesenteric fat, muscle and injection sites, respectively. The tissue concentrations of OTC residues were below the established cattle tolerances for OTC in liver (6 p.p.m.), muscle (2 p.p.m.) and kidney (12 p.p.m.) by 48 h, and in injection site muscle by 14 days after the single i.m. injection of 20 mg/kg.     

Colostral transfer of gamma glutamyl transferase in lambs

Serum gamma glutamyl transferase (GGT) levels in blood samples taken from normal lambs which had suckled colostrum were found to be up to 140 times normal adult levels. These high serum levels declined rapidly reaching a stable level approximately 60% higher than normal adult values by 24 days of age. Newborn lambs which had not yet consumed colostrum had GGT levels which would be considered normal in adult sheep. The GGT concentration in ewes' colostrum was up to 470 times normal serum levels. There was a significant positive correlation between serum GGT and gamma globulin levels in blood samples taken from lambs within 24 hours of birth.

Lambs' serum alkaline phosphatase (AP) and serum glutamate oxaloacetate transaminase (SGOT) levels also rose concurrently with the absorption of colostral gamma globulin, with the day 1 AP values being significantly correlated with the serum gamma globulin levels. Serum AP levels declined gradually but were still well above normal adult levels at 45 days of age while SGOT levels returned to normal adult levels by two to three days after birth.

It is concluded therefore that, as previously shown in calves, lambs acquire high levels of serum GGT activity from their mothers' colostrum in proportion to the amount of gamma globulin absorbed and also show a concurrent rise in serum AP activity. However the rise in SGOT levels at this time has not been observed in calves.     

Measurement of certain plasma and serum enzymes in the horse

The study of the use of serum or plasma enzymes in the horse is reviewed.

Analyses of such enzymes in the horse have been performed mainly for the detection and monitoring of abnormalities which affect liver tissue and muscle fibres. Examples of muscle disorders are post-anaesthetic forelimb lameness and the clinical myopathy syndrome which varies from a mild “tying-up” to a severe paralytic myoglobinuria (EPM). Measurements have also been made during training periods in an endeavour to assess the effects of exercise on muscle tissue. One of the benefits of such a study could be the prediction of the period of optimum performance.

The two enzymes most frequently used for. muscle studies have been glutamic oxaloacetic transaminase (GOT) (aspartate aminotransferase) and creatine Phosphokinase (CPK). The former, while not muscle specific and less sensitive than CPK to small amounts of muscle tissue damage, has a slower clearance rate from blood than CPK. Determination of both enzymes together has some advantages in determining the prognosis in cases with severe muscle damage. Later studies have included aldolase, which is a sensitive skeletal muscle specific enzyme and lactic dehydrogenase (LDH), which is widely distributed by various tissues at high concentrations. Most of the work on serum LDH has centred on its separation into 5 isoenzymes, and on relating the isoenzyme pattern to the various tissues. More studies on this, and on the isoenzymes of CPK, are required.

Apart from cost, one of the major problems in enzymology has been lack of a standardisation of laboratory methods which has led to a wide range of published normal values. Reliance on such values may lead to difficulties in interpretation, particularly when serum changes are small.     

Pharmacokinetics of clindamycin HCl administered intravenously, intramuscularly and subcutaneously to dogs

A buffered aqueous solution of clindamycin Hcl (200 mg/mL) was injected intravenously (i.v.) intramuscularly (i.m.) and subcutaneously (s.c.) in a non-randomized, partial cross-over trial involving six male and six female dogs. Blood samples were collected at conventional, predetermined time periods and serum drug concentrations were determined by microbiological assay. Dogs were observed clinically for signs of pain, and activity of serum creatine phosphokinase (CPK) was monitored after i.m. dosing. The i.v. data from five of the dogs best fitted a two-compartment open-system pharmacokinetic model whereas a non-compartment model was most suitable for analysis of the data from the remaining seven dogs. The mean i.v. elimination half-life (t1/2 beta) and the mean residence time (MRT) were 124 and 143 min, respectively. The mean volume of distribution at steady state (Vss) was 0.86 L/kg. Little pain was recorded upon i.m. injection; mean peak serum drug concentration (Cmax) was 4.4 micrograms/mL, the elimination half-life (t1/2el) was 247 min and the calculated bioavailability (F) was 115% of the i.v. dose. Serum CPK activity was elevated to 25-fold the pretreatment level in samples collected 4, 8 and 12 h after i.m. injection. Pain was not recorded after s.c. drug administration; the mean Cmax of 20.8 micrograms/mL was significantly greater than the corresponding value for the i.m. route, and F was 310%. The s.c. route appears to be superior to the i.m. route in terms of local tolerance and serum drug level; a 10 mg/kg SID treatment regimen is suggested for treatment of canine infections due to clindamycin sensitive bacteria.     

Serum enzyme activity evaluated in budgerigars (Melopsittacus undulatus) inflicted with muscle injury

Aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations were measured in 73 budgerigars. In spite of increases in the serum concentration of AST and ALT the loss of enzyme activity from the injection site occurred at about the same rate for all four enzymes tested. The rate constants, calculated in birds administered muscle extract via the intravenous or the intramuscular route of injection, disclosed that in subjects treated intramuscularly the serum enzyme elevation was dependent on the elimination half-life of the enzyme and partly on the rate at which the particular enzyme was absorbed into the bloods-tream. Moreover, serum enzyme elevations correlated inversely with total clearance. To determine the aetiology of blood enzyme elevation in budgerigars, for diagnostic purposes, the absorption rate, total clearance and elimination half-life of each of these four enzymes are deemed valuable components.     

Ruminal excretion of sulfadimethoxine and sulfadimethyloxazole in goats and their influence on some enzyme activities and renal clearances

Five clinically health goats were injected with sulfadimethoxine and sulfadimethyloxazole in a single dose of 100 mg/kg b. wt. by intravenous route. Highest concentration levels of sulfadimethoxine and sulfadimethyloxazole in rumen were detected 1 hour following intravenous injection, then the concentration for both compounds declined at 12 and 8 hours post administration, respectively. In addition, both types of sulfonamide completely disappeared in ruminal fluid samples taken after 24 and 12 hours, respectively. The rate of acetylation for sulfadimethoxine and sulfadimethyloxazole were nearly similar and occurred to a high extent in ruminal fluid (22.95 and 23.72%, respectively). On the other hand, both tested drugs increased significantly the ruminal gas production from the first to eight hours after i.v. injection in goats. Changes in the serum enzyme activities (SGOT, SGPT and alkaline phosphatase) observed with sulfadimethoxine and sulfadimethyloxazole, and represented by a significant decrease in the activity of SGOT and SGPT level, alkaline phosphatase 4 hours sulfadimethoxine and in GOT/GPT ratio 24 and 48 hours after i.v. injection, respectively. The creatinine clearance was significantly decreased after 4 hours following the i.v. administration of sulfadimethoxine and sulfadimethyloxazole in goats.     

Serum folates during the reproductive cycle of sows

In a first trial, serum folates concentration was measured in 105 sows randomly distributed into seven groups of 15 animals each. Each group represented one time period of the reproductive cycle: weaning, mating, 15, 30, 60, 90 and 110 d of gestation. The average serum folates concentrations for the different groups of sows were, expressed as ng/ml +/- SE, 99.5 +/- 8.9, 68.5 +/- 9.6, 63.9 +/- 7.4, 59.5 +/- 5.7, 39.6 +/- 5.7, 45.3 +/- 5.8 and 49.1 +/- 6.3, respectively. Results showed a biphasic decrease in serum folates levels, first at mating and then at 60 d of gestation. These results indicate a possible deficiency in serum folates during mid-gestation. In a second trial, 20 sows were assigned randomly to four groups of five animals each, representing four time periods of the reproductive cycle: weaning, mating, 30 and 60 d of gestation. One intramuscular injection of 15 mg folic acid was administered to all sows and serum folates concentration was measured before the injection and at 2-d intervals during a period of 14 d after the injection. An increase in serum folates was noted in sows of all groups. The time response curves observed after the injection are presented and discussed. The decrease in folates levels observed during early and mid-gestation could be moderated by im administration of this vitamin.     

Some enzyme interrelationships in serum and organs of Egyptian camel

In 7 normal healthy Egyptian one-humped camels aged 3-4 years, the relationships were studied between enzyme activities of lactic dehydrogenase (LDH), creatine phosphokinase (CPK), alkaline phosphatase (ALP), acid phosphatase (ACP), and cholonesterase (CHE) of serum and organs as well as between ACP and ALP and between LDH and CPK. Liver, heart, kidney, and spleen tissue samples as well as serum were analysed for total enzyme activity. The following results were obtained: --The heart was the organ with the highest activities of ALP, LDH, and CPK, and it contained high values of CHE, whereas the lowest activities of all enzymes were recorded from serum. The spleen exhibited of the highest activity of ACP. --Each of the serum enzymes ALP, LDH, and CHE were in strong inverse relationship with the corresponding enzymes in the liver. Strong inverse relationships existed also between serum LDH and kidney LDH as well as between CPK in serum and heart. --Direct relationships were remarkable serum LDH and that of spleen and heart as well as between serum ACP and that of liver and heart. --Interrelationships were inverse between ACP and ALP in liver, kidney, and heart, but weak direct interrelationships were characteristic between the 2 enzymes in serum and spleen. --LDH was inversely interrelated with CPK in serum and heart.     

Dystrophin-deficient muscular dystrophy in a Toy Poodle with a single base pair insertion in exon 45 of the Duchenne muscular dystrophy gene

A 10-month-old, intact male Toy Poodle was referred for a postural abnormality. Blood biochemical tests revealed a marked increase in plasma creatine phosphokinase (CPK) concentration. The isoenzyme test showed that 99% of serum CPK consisted of CPK-MM. Histopathological evaluation of muscle biopsy samples confirmed scattered degeneration and necrosis of myofibers. Immunohistochemistry for dystrophin showed an absence of staining in muscle cells. Based on these findings, the dog was diagnosed with dystrophin-deficient muscular dystrophy. Whole genome sequencing using genomic DNA extracted from blood revealed a single base pair insertion in exon 45 of the Duchenne muscular dystrophy (DMD) gene. This is the first report on muscular dystrophy in Toy Poodles and identified a novel mutation in the DMD gene.     

Transport versus on-farm slaughter of bison: Physiological stress,animal welfare,and avoidable trim losses

Ranched bison are typically less acclimated to handling than are domesticated livestock, suggesting that they might be more vulnerable to handling and transportation stressors. Grain-finished bison were slaughtered on-farm (n = 11), or held for 48 h, transported to a research abattoir, held in lairage for 18 h, and then slaughtered (n = 11). An additional group (n = 10) was sampled at a conventional fixed location abattoir. Measures included serum cortisol and corticosterone concentrations during on-farm handling and exsanguination, serum glucose, creatinine phosphokinase (CPK), aspartate aminotransferase (AST), and trim losses. Transport was associated with an increase in trim loss. On-farm, glucose was elevated, CPK was positively associated with handling order over 12 h, and corticosterone concentration, although lower than cortisol concentration, showed a greater response to prolonged disturbance. With appropriate on-farm handling facilities, the use of on-farm slaughter and mobile abattoir could avoid muscle damage and trim losses, and mitigate injuries sustained during handling and transport of bison.     

Serum concentrations of etorphine in juvenile African elephants

Eleven juvenile African elephants were given etorphine hydrochloride (2.19 +/- 0.11 micrograms/kg of body weight; mean +/- SD) as a single IM injection; 3 elephants were given additional etorphine (0.42 +/- 0.09 micrograms/kg) IV. After immobilization, each elephant was maintained in lateral recumbency by administration of a 0.5% halothane/oxygen mixture or by administration of multiple IV injections of etorphine. At postinjection hours 0.25 and 0.5 and at 30-minute intervals thereafter, blood samples were collected via an auricular artery, and serum concentrations of etorphine were determined by use of radioimmunoassay. The highest mean serum concentration of etorphine in 6 elephants given a single IM injection and subsequently maintained on halothane and oxygen was 1.62 +/- 0.97 ng/ml at postinjection hours 0.5; thereafter, the mean serum concentration decreased steadily. In 4 elephants maintained in lateral recumbency with multiple IV administrations of etorphine, a correlation was not found between the time to develop initial signs of arousal and serum concentrations of etorphine before arousal. After administration of the initial immobilizing dose of etorphine, the interval between successive IV administrations of etorphine decreased.     

Serum disposition of exogenous progesterone after intramuscular administration in bitches

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

Relationship between liver degeneration and the production of dark firm dry meat in slaughtered pigs

Sixty-five of 77 slaughtered pigs with liver degeneration produced dark firm dry (DFD) meat. The biochemical properties of blood, liver and muscle of those pigs were examined. In the blood, the NEFA level was higher, which indicated the mobilization of lipids from adipose tissues. The serum CPK and LDH5 levels were higher, the enzymes being derived from muscle. In the degenerative liver with yellowish discoloration, the TG level was higher and the glycogen level was lower than in a normal liver. In the DFD muscle with the final pH above 6.0, both the glycogen level immediately after slaughter and the lactic acid level 24 hr after slaughter were lower than in a normal muscle with the final pH below 6.0. Five pigs exhausted experimentally by 53-hr fasting and hard exercise showed the same changes in the blood and liver as the pigs with liver degeneration. Four of the 5 exhausted pigs showed the same changes in the muscle as in DFD meat. From these data, it was confirmed that exhaustion before slaughter led to lipid accumulation in the liver and to a decrease in muscle glycogen, and consequently caused both liver degeneration and DFD meat in the same pig.     

Serum alpha-tocopherol concentration in sheep after intramuscular injection of DL-alpha-tocopherol.

Forty-three crossbred wethers weighing 35 to 60 kg were used to investigate the effect of a single i.m. injection of DL-alpha-tocopherol (DL-alpha-ol). Animals were offered 1 kg/d of a basal diet containing 25 ppm of vitamin E. Lambs were randomly assigned to one of five DL-alpha-ol injection treatments as follows: 1) control (placebo, 0 IU), 2) 125 IU, 3) 250 IU, 4) 500 IU, or 5) 1,000 IU. Blood samples were taken via jugular venipuncture on d 1 before treatment administration and thereafter at designated intervals up to 360 h postinjection. The i.m. injections of DL-alpha-ol irrespective of dose increased serum alpha-tocopherol. Results showed a dose x time interaction (P less than .0001) across all treatments. Serum alpha-tocopherol increased rapidly to maximum concentration during the first 8 to 12 h for all non-zero treatments, followed by a rapid decline to pretreatment values. The mean serum alpha-tocopherol concentration at 0 h was .69 microgram/mL. Estimated peak serum alpha-tocopherol concentrations +/- SE were 6.68 +/- 1.04, 9.62 +/- 1.04, 21.66 +/- 2.37, and 50.75 +/- 7.05 micrograms/mL for Treatments 2 through 5, respectively. Results showed a quadratic dose effect (P less than .0003) on maximum response with apparently no effect on time taken to reach this peak. There was also a quadratic dose effect (P less than .0001) on the area under the concentration-time curve. The time taken for serum alpha-tocopherol to return to pretreatment levels increased with dose (56, 64, 67, and 74 h, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

肌注PHA对犬血清中补体C3、C4的影响

为研究植物凝集素(PHA)对各犬血清中补体C3、C4浓度的影响,试验分成4个组:低剂量组(0.05 mg/kg)、中剂量组(0.10 mg/kg)、高剂量组(0.20 mg/kg)、对照组,对犬进行肌肉注射。在注射前和注射后的7 d、14 d对各组犬进行采血测定其血清中补体的含量,并进行统计分析。结果:中剂量组可显著提高机体的补体水平(P<0.05),并在高水平维持较长时间;低剂量组和高剂量组作用不显著(P>0.05)。     

新疆瘦肉型新品种猪血清CPK活力与肌肉性状的关系

在新疆瘦肉型新品种猪培育期间，选择三个不同品系，连续三个世代，分别测定了供试猪的ＣＰＫ（磷酸肌酸激酶）活力、背膘厚度与眼肌厚度，探讨了它们之间的关系，结果表明：各品系猪经三个世代选择，ＣＰＫ活力逐代呈上升趋势，各世代之间均差异显著（Ｐ〈０．０１）；三世代与一世代相比，平均背膘厚度减少０．５１ｃｍ，眼肌厚度增加０．５４ｃｍ，差异显著（ｐ〈０．０５，Ｐ〈０．０１）；新品种猪试验全期ＣＰＫ活力与背膘厚度