Pharmacokinetic profiles of the active metamizole metabolites in healthy horses

Metamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine and dogs. MT is rapidly hydrolysed to the active primary metabolite 4‐methylaminoantipyrine (MAA). MAA is formed in much larger amounts compared with other minor metabolites. Among the other secondary metabolites, 4‐aminoantipyrine (AA) is also relatively active. The aim of this research was to evaluate the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.) and intramuscular (i.m.) routes in healthy horses. Six horses were randomly allocated to two equally sized treatment groups according to a 2 × 2 crossover study design. Blood was collected at predetermined times within 24 h, and plasma was analysed by a validated HPLC‐UV method. No behavioural changes or alterations in health parameters were observed in the i.v. or i.m. groups of animals during or after (up to 7 days) drug administration. Plasma concentrations of MAA after i.v. and i.m. administrations of MT were detectable from 5 min to 10 h in all the horses. Plasma concentrations of AA were detectable in the same range of time, but in smaller amounts. Maximum concentration (C_max), time to maximum concentration (T_max) and AUMC_0‐last of MAA were statistically different between the i.v. and i.m. groups. The AUC_IM/AUC_IV ratio of MAA was 1.06. In contrast, AUC_0‐last of AA was statistically different between the groups (P < 0.05) with an AUC_IM/AUC_IV ratio of 0.54. This study suggested that the differences in the MAA and AA plasma concentrations found after i.m. and i.v. administrations of MT might have minor consequences on the pharmacodynamics of the drug.     

Pharmacokinetic Assessment of the Marker Active Metabolites 4-Methyl-amino-antipyrine and 4-Acetyl-amino-antipyrine After Intravenous and Intramuscular Injection of Metamizole (Dipyrone) in Healthy Donkeys

Metamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine, and dogs in some countries. Metamizole is rapidly hydrolyzed to the active primary metabolite 4-methyl-amino-antipyrine (MAA). MAA is formed in much larger amounts compared to other minor metabolites. Among the other secondary metabolites, 4-amino-antipyrine (AA) is also relatively active. The aim of this research was to evaluate the pharmacokinetic profiles of MAA and AA after administration of 25 mg/kg MT by intravenous (IV) and intramuscular (IM) routes in healthy donkeys. Six jennies were randomly allocated to two equally sized treatment groups according to a 2 × 2 crossover study. Blood was collected at predetermined times within 24 hours, and plasma was analyzed by a validated HPLC UV method. Plasma concentrations of MAA after IV and IM administrations of MT were detectable from 5 minutes to 10 hours in all the donkeys. Plasma concentrations of AA were detectable from 5 minutes to 8 hours, but in smaller amounts. C_max (P < .01), AUC_0-last, AUC_0-∞, AUMC_0-last, and MRT (P < .05) were statistically different between the IV and IM groups. The AUC_IM/AUC_IV ratio of MAA was 1.37. The AA concentrations were lower than those found for MAA. The AA plasma versus time curves profiles after the two routes of administration of MT were variable (within the groups) and different (between the groups). T_max, λz, and AUC_0-last were found to be statistically different between the groups (P < .05). The AUC_IM AA/AUC_IV AA ratio was 2.26.     

Pharmacokinetic profiles of the active metamizole metabolites after four different routes of administration in healthy dogs

Metamizole (MT), an analgesic and antipyretic drug, is rapidly hydrolyzed to the active primary metabolite 4‐methylaminoantipyrine (MAA) and relatively active secondary metabolite 4‐aminoantipyrine (AA). The aim of this study was to assess the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.), intramuscular (i.m.), oral (p.o.), and rectal (RC) routes in dogs. Six dogs were randomly allocated to an open, single‐dose, four‐treatment, four‐phase, unpaired, crossover study design. Blood was collected at predetermined times within 24 hr, and plasma was analyzed by a validated HPLC‐UV method. Plasma concentrations of MAA and AA after i.v., i.m., p.o., and RC administrations of MT were detectable from 5 (i.v. and i.m.) or 30 (p.o. and RC) min to 24 hr in all dogs. The highest concentrations of MAA were found in the i.v., then i.m., p.o., and RC groups. Plasma concentrations of AA were similar for i.v., i.m., and RC, and the concentrations were approximately double those in the PO groups. The AUC_EV/IV ratio for MAA was 0.75 ± 0.11, 0.59 ± 0.08, and 0.32 ± 0.05, for i.m., p.o., and RC, respectively. The AUC_EV/IV ratio for AA was 1.21 ± 0.33, 2.17 ± 0.62, and 1.08 ± 0.19, for i.m., p.o., and RC, respectively. Although further studies are needed, rectal administration seems to be the least suitable route of administration for MT in the dog.     

Meloxicam pharmacokinetics using nonlinear mixed‐effects modeling in ferrets after single subcutaneous administration

This study was designed to investigate the pharmacokinetics of meloxicam, an oxicam class, nonsteroidal anti‐inflammatory drug (NSAID), in ferrets. We determined the pharmacokinetic properties of a single subcutaneous dose of meloxicam (0.2 mg/kg) in nine male and nine female ferrets. Blood samples were collected by venipuncture of the cranial vena cava into heparinized syringes. Plasma meloxicam concentrations were determined by high‐pressure liquid chromatography (HPLC). Pharmacokinetic variables were calculated using nonlinear mixed‐effects modeling to take advantage of the population‐based sampling scheme and to minimize sample volume collected per animal. Maximum plasma concentration, volume of distribution per absorption, and elimination half‐life were 0.663 μg/mL, 0.21 L, and 11.4 h, respectively, for females and 0.920 μg/mL, 0.35 L, and 17.8 h, respectively, for males. Significant differences were found in each of the above parameters between male and female ferrets. Systemic clearance per absorption was not affected by gender and was 13.4 mL/h. Analgesic efficacy was not evaluated, but plasma meloxicam concentrations achieved in these animals are considered effective in other species. Sex differences in the pharmacokinetic behavior of meloxicam should be taken into consideration when treating ferrets.     

Pharmacokinetic profiles of metamizole (dipyrone) active metabolites in goats and its residues in milk

Metamizole (dipyrone, MET) is a nonopioid analgesic drug commonly used in human and veterinary medicine. The aim of this study was to assess two major active metabolites of MET, 4‐methylaminoantipyrin (MAA) and 4‐aminoantipyrin (AA), in goat plasma after intravenous (IV) and intramuscular (IM) administration. In addition, metabolite concentration in milk was monitored after IM injection. Six healthy female goats received MET at a dose of 25 mg/kg by IV and IM routes in a crossover design study. The blood and milk samples were analyzed using HPLC coupled with ultraviolet detector and the plasma vs concentration curves analyzed by a noncompartmental model. In the goat, the MET rapidly converted into MAA and the mean maximum concentration was 183.97 μg/ml (at 0.08 hr) and 51.94 μg/ml (at 0.70 hr) after IV and IM administration, respectively. The area under the curve and mean residual time values were higher in the IM than the IV administered goats. The average concentration of AA was lower than MAA in both groups. Over 1 μg/ml of MAA was found in the milk (at 48 hr) after MET IM administration. In conclusion, IM is considered to be a better administration route in terms of its complete absorption with long persistence in the plasma. However, this therapeutic option should be considered in light of the likelihood of there being milk residue.     

Dietary lysine requirement for 7–16 kg pigs fed wheat–corn–soybean meal‐based diets

Two experiments were conducted to determine the lysine requirement of weaned pigs [Duroc × (Yorkshire × Landrace)] with an average initial BW of 7 kg and fed wheat–corn–soybean meal‐based diets. The experiments were conducted for 21 days during which piglets had free access to diets and water. Average daily gain (ADG), average daily feed intake (ADFI) and gain to feed ratio (G:F) were determined on day 7, 14 and 21. Blood samples were collected on day 0 and 14 to determine plasma urea nitrogen (PUN) concentration. In experiment 1, 96 weaned pigs were housed four per pen and allocated to four dietary treatments with six replicates per treatment. The diets contained 0.99%, 1.23%, 1.51% and 1.81% standardized ileal digestible (SID) lysine, respectively, corrected analysed values. The rest of the AA were provided to meet the ideal AA ratio for protein accretion. Increasing dietary lysine content linearly increased (p < 0.05) ADG and G:F. In experiment 2, 90 piglets were housed three per pen and allocated to five dietary treatments with six replicates per treatment. The five diets contained 1.03%, 1.25%, 1.31%, 1.36% and 1.51% SID lysine, respectively, corrected analysed values. Increasing dietary lysine content linearly increased (p < 0.05) G:F, linearly decreased (p < 0.05) day‐14 PUN and quadratically (p < 0.05) increased ADG and ADFI. The ADG data from experiment 2 were subjected to linear and quadratic broken‐lines regression analyses, and the SID lysine requirement was determined to be 1.29% and 1.34% respectively. On average, optimal dietary SID lysine content for optimal growth of 7–16 kg weaned piglets fed wheat–corn–SBM‐based diets was estimated to be 1.32%; at this level, the ADG and ADFI were 444 and 560 g, respectively, thus representing an SID lysine requirement, expressed on daily intake basis as, 7.4 g/day or 16.76 mg/g gain.     

Polymorphism in promoter region of growth hormone receptor is associated with potential production capacity of insulin‐like growth factor‐1 in pre‐pubertal Holstein heifers

Insulin‐like growth factor‐1 (IGF‐1) is one of the important factors for growth, milk production and reproductive functions and mainly released from the liver in response to growth hormone (GH) via GH receptor (GHR) in cattle. Recently, some single nucleotide polymorphisms (SNPs) were identified in the bovine GHR gene. Some GHR‐SNPs were shown to be related to plasma IGF‐1 concentration in cattle. Hence, the capacity to IGF‐1 production in the liver might be affected by GHR‐SNP and associated with performance in the future. This study examined whether GHR‐SNP is associated with IGF‐1 production in the liver of pre‐pubertal heifers. In 71 Holstein calves, blood samples for genomic DNA extraction were obtained immediately after birth. To genotype the GHR‐SNPs in the promoter region, polymerase chain reaction (PCR) products were digested with restriction enzyme NsiI (cutting sites: AA, AG and GG). All heifers at 4 months of age were intramuscularly injected with 0.4 mg oestradiol benzoate. Blood samples were obtained from the jugular vein just before (0 h) and 24 h after injection. The number of AA, AG and GG at the NsiI site was 0, 17 and 54 respectively. In AG and GG, plasma GH concentrations were higher pre‐injection than 24 h post‐injection (p < 0.01). Moreover, plasma GH concentrations in AG post‐injection were higher than in GG (p < 0.05). In contrast, the GG genotype exhibited higher plasma IGF‐1 concentrations in pre‐injection than post‐injection (p < 0.01), although oestradiol did not change IGF‐1 concentration in the AG genotype. We conclude that the GG polymorphism in the promoter region of GHR is associated with a higher potential capacity of IGF‐1 production in the liver of cattle.     

Pharmacokinetic profiles of the two major active metabolites of metamizole (dipyrone) in cats following three different routes of administration

This study was performed to determine pharmacokinetic profiles of the two active metabolites of the analgesic drug metamizole (dipyrone , MET), 4‐methylaminoantipyrine (MAA), and 4‐aminoantipyrine (AA), after intravenous (i.v., intramuscular (i.m.), and oral (p.o.) administration in cats. Six healthy mixed‐breed cats were administered MET (25 mg/kg) by i.v., i.m., or p.o. routes in a crossover design. Adverse clinical signs, namely salivation and vomiting, were detected in all groups (i.v. 67%, i.m. 34%, and p.o. 15%). The mean maximal plasma concentration of MAA for i.v., i.m., and p.o. administrations was 148.63 ± 106.64, 18.74 ± 4.97, and 20.59 ± 15.29 μg/ml, respectively, with about 7 hr of half‐life in all routes. Among the administration routes, the area under the plasma concentration curve (AUC) value was the lowest after i.m. administration and the AUC_EV/i.v. ratio was higher in p.o. than the i.m. administration without statistical significance. The plasma concentration of AA was detectable up to 24 hr, and the mean plasma concentrations were smaller than MAA. The present results suggest that MET is converted into the active metabolites in cats as in humans. Further pharmacodynamics and safety studies should be performed before any clinical use.     

Pharmacokinetic parameters for single‐ and multi‐dose regimens for subcutaneous administration of a high‐dose ceftiofur crystalline‐free acid to neonatal foals

The objective of this study was to determine the pharmacokinetics of single‐ and multi‐dose ceftiofur crystalline‐free acid (CCFA) administered subcutaneously at a dose of 13.2 mg/kg to 12 neonatal foals 1–3 days of age. Six foals received a single subcutaneous dose, while 6 additional foals received 4 doses of CCFA at 48‐h intervals. Blood samples were collected at pre‐determined times following drug administration, and plasma concentrations of ceftiofur free acid equivalents (CFAE) were measured using high‐performance liquid chromatography. Following single‐dose administration of CCFA, the mean ± standard deviation maximum observed plasma concentration was 3.1 ± 0.6 μg/mL and observed time to maximal plasma concentration was 14.0 ± 4.9 h. Following multi‐dose administration of CCFA, the mean ±standard deviation times above CFAE concentrations of ≥0.5 μg/mL and ≥2.0 μg/mL were 192.95 ± 15.86 h and 78.80 ± 15.31 h, respectively. The mean ± standard deviation area under the concentration vs time curve (AUC_0→∝) was 246.2 ± 30.7 h × μg/mL and 172.7 ± 27.14 h × μg/mL following single‐ and multi‐dose CCFA administrations, respectively. Subcutaneous administration of CCFA at 13.2 mg/kg in neonatal foals was clinically well‐ tolerated and resulted in plasma concentrations sufficient for the treatment of most bacterial pathogens associated with neonatal foal septicemia. Multi‐dose administration of four doses at dosing interval of 48 h between treatments maintains appropriate therapeutic concentrations in neonatal foals.     

A holstein cow–calf model for the transfer of ciprofloxacin through milk after a long‐term intravenous infusion

This study is part of an ongoing effort to develop animal models that provide milk and sufficient infant (offspring) plasma samples to fully describe a drug's pharmacokinetics to quantitate the risk to the nursing infant. Ciprofloxacin was administered to six healthy Holstein cows as a constant rate intravenous infusion (flow rate was weight adjusted) to achieve a steady‐state concentration of approximately 300 ng/mL for 7 days. Plasma and milk samples were collected from the cow at regular intervals over the course of the 7 days. The plasma and milk samples were analyzed for ciprofloxacin by high‐performance liquid chromatography. The milk was fed to calves, and calf plasma samples were analyzed to study the lactational transfer of ciprofloxacin from dam to nursing neonate. Remarkably, concentrations of ciprofloxacin in milk were 45 times higher than plasma drug concentrations in the dam. Approximately 6% of the administered dose was transferred to the milk, resulting in an average oral dose of 0.5 mg/kg to the calves with every feeding. The drug did not accumulate in the calves, and plasma concentrations were between one‐tenth and one‐fifth the plasma concentrations of the dam.     

Plasma concentration‐dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone‐21‐isonicotinate

Detection times and screening limits (SL) are methods used to ensure that the performance of horses in equestrian sports is not altered by drugs. Drug concentration–response relationship and knowledge of concentration–time profiles in both plasma and urine are required. In this study, dexamethasone plasma and urine concentration–time profiles were investigated. Endogenous hydrocortisone plasma concentrations and their relationship to dexamethasone plasma concentrations were also explored. A single dose of dexamethasone‐21‐isonicotinate suspension (0.03 mg/kg) was administered intramuscularly to six horses. Plasma was analysed for dexamethasone and hydrocortisone and urine for dexamethasone, using UPLC‐MS/MS. Dexamethasone was quantifiable in plasma for 8.3 ± 2.9 days (LLOQ: 0.025 μg/L) and in urine for 9.8 ± 3.1 days (LLOQ: 0.15 μg/L). Maximum observed dexamethasone concentration in plasma was 0.61 ± 0.12 μg/L and in urine 4.2 ± 0.9 μg/L. Terminal plasma half‐life was 38.7 ± 19 h. Hydrocortisone was significantly suppressed for 140 h. The plasma half‐life of hydrocortisone was 2.7 ± 1.3 h. Dexamethasone potency, efficacy and sigmoidicity factor for hydrocortisone suppression were 0.06 ± 0.04 μg/L, 0.95 ± 0.04 and 6.2 ± 4.6, respectively. Hydrocortisone suppression relates to the plasma concentration of dexamethasone. Thus, determination of irrelevant plasma concentrations and SL is possible. Future research will determine whether hydrocortisone suppression can be used as a biomarker of the clinical effect of dexamethasone.     

Pharmacokinetics of tramadol and its major metabolite after intramuscular administration in piglets

Tramadol (T) is a centrally acting atypical opioid used for treatment of dogs. Piglets might experience pain following castration, tooth clipping and tail docking and experimental procedures. The aim of this study was to assess the pharmacokinetics of T and its active metabolite M1 in male piglets after a single intramuscular injection. Six healthy male piglets were administered T (5 mg/kg) intramuscularly. Blood was sampled at scheduled time intervals and drug plasma concentrations evaluated by a validated HPLC method. T plasma concentration was quantitatively detectable from 0.083 to 8 h. M1 was quantified over a shorter time period (0.083–6 h) with a T_max at 0.821 h. The study demonstrated that piglets produce a larger amount of M1 compared with dogs, horses and goats. The human minimum effective concentration of M1 (40 ng/mL) was exceeded for over 3 h in piglets. If it is assumed to also apply to piglets, it could be speculated that the drug efficacy might exert its action over 3 h or longer. This assumption has to be confirmed by further specific pharmacokinetic/pharmacodynamic studies.     

Subcutaneous meloxicam suspension pharmacokinetics in mice and dose considerations for postoperative analgesia

Meloxicam is a cyclooxygenase (COX) inhibitor with a higher selectivity for cyclooxygenase‐2 (COX‐2) than for cyclooxygenase‐1 (COX‐1). In the laboratory setting, this nonsteroidal anti‐inflammatory drug (NSAID) is commonly selected for analgesia in mice and administered every 24 h. This study characterizes the plasma concentration achieved from a dose of 1.6 mg/kg of meloxicam administered once every 24 h subcutaneously for 72 h in male and female C57BL/6 mice. These values were compared, over time, to reference COX‐2 inhibition constants for meloxicam. No significant differences in trough plasma concentrations were noted between genders. The plasma concentrations were below the COX‐2 IC₅₀ after 12 h. To maintain a plasma concentration at or above the COX‐2 whole blood IC_50, the study results suggest an administration frequency of every 12 h when using a dose of 1.6 mg/kg in C57BL/6 mice.     

The immediate effects of weaning stress on the hypothalamus‐pituitary‐adrenal alteration of newly weaned piglets

This study was conducted to examine the effects of weaning stress on gene expression of specific markers in hypothalamus‐pituitary‐adrenal (HPA) axis and neuronal activity in the newly weaned piglets. Twelve 28‐days‐old, newly weaned crossbred (Landrace × Yorkshire × Duroc) male piglets from 6 l (2 piglets/l) were randomly categorized into two groups: (a) weaning stress: piglets were separated from their dams, relocated and mixed with the unacquainted domestic piglets for 2 hr (stress, n = 6); (b) no‐stress: piglets stayed with their dams in the farrowing house (NS; n = 6). After weaning stress, all piglets were electrically euthanized and the blood samples/HPA tissues were collected for subsequent analysis, including plasma cortisol and mRNA expression of c‐fos, c‐jun, corticotropin‐releasing hormone (CRH), CRH receptor 1 (CRHR‐1) and adrenocorticotropin hormone receptor (MC2R). Results: Weaning stress significantly (p < 0.05) increased the plasma cortisol level and suppressed the expression of c‐fos and CRH in hypothalamus. In addition, weaning stress enhanced the mRNA abundance of c‐jun and CRHR‐1 in the pituitary gland. No significant differences in the gene expression of MC2R and CRHR‐1 were observed in the adrenal gland between treatment groups. Taken together, HPA involved in weaning stress and CRHR‐1 and c‐jun could be potential markers to evaluate the activation of HPA axis.     

Pharmacokinetics of single‐dose oral ponazuril in weanling goats

Ponazuril (toltrazuril sulfone) is a triazine antiprotozoal agent that targets apicomplexan organisms. Ponazuril may have clinical application in the treatment of clinical coccidiosis due to Eimeria species in goats, along with other protozoal infections. To evaluate the absorption, distribution and elimination characteristics of ponazuril in goats, a sensitive, validated high‐pressure liquid chromatography and mass spectroscopy method for ponazuril in caprine plasma was developed. After a single oral dose of ponazuril at 10 mg/kg, plasma samples from seven weanling goats were collected and assayed. Plasma concentrations of ponazuril in the goats peaked at 36 ± 13 h post drug administration at a concentration of 9 ± 2 μg/mL. Concentrations declined to an average of 4.2 ± 0.8 μg/mL after 168 h with an average elimination half‐life of 129 ± 72 h post drug administration. This study shows that ponazuril is relatively well absorbed after a single oral dose in goats. Efficacy trials are underway to determine clinical efficacy of ponazuril in the treatment of clinical coccidiosis in goats at 10 mg/kg dosage.     

Effects of sinomenine in LPS‐associated diseases are related to inhibition of LBP,Mac‐1, and L‐selectin levels

The aim of the research was to investigate the anti‐endotoxin and anti‐inflammatory effects of Sinomenine, an agent commonly found in Chinese herbal medicines. Endotoxin (i.e., 1 mg lipopolysaccharide (LPS)/kg)) was administered via intraperitoneal (IP) injection to piglets in high‐, middle‐, and low‐dose sinomenine groups. Piglets were then treated with 1, 5 or 10 mg/kg sinomenine, intramuscularly (i.m.), 3 hr after LPS. Vehicle was administered, as above, to drug control group piglets followed 3 hr later by 10 mg/kg sinomenine i.m.. LPS control group piglets were challenged with 1 mg/kg LPS IP, followed by vehicle i.m., and naïve control piglets were treated with normal saline IP, followed by normal saline i.m., as above. Temperatures were measured, and blood samples were collected from the precaval veins of piglets at 12, 24, and 48 hr post‐LPS or vehicle injection. Clinical signs were recorded, and index levels were analyzed via ELISA. Sinomenine was found to reduce the incidence and severity of LPS‐induced toxicities, including body temperature elevation, cell adhesion, and systemic inflammation. These data suggest that sinomenine may be effective for regulating inflammatory responses and has the potential for use as an anti‐endotoxin therapy.     

The effect of sex on antipyrine metabolism in cattle at different ages

The aim of this study was to determine the effect of sex on the metabolism of antipyrine by measuring the antipyrine plasma clearance as well as excretion of three major metabolites in urine in cattle of different ages. The experiment was carried out on 10 female and 10 male cattle of Black and White breed. The antipyrine test was carried out at 1, 2, 4, 6, 8, 12 and 18 months of age for each animal (single dose of 10 mg/kg antipyrine were given intravenously). The concentrations of antipyrine, 4-hydroxyantipyrine (4-OHA), 3-hydroxymethylantipyrine (HMA) and norantipyrine (NORA) were measured in plasma and urine by high performance liquid chromatography (HPLC). The apparent volume of distribution of antipyrine (aVd) decreased significantly between 1 and 18 months of age, but mean aVd values observed in males and females were not statistically different. The experimental period was characterised by a steady decrease (statistically significant) in antipyrine half-life (t1/2beta). These values did not differ significantly between males and females under 12 months. In 12 and 18 month-old animals the antipyrine half-life in the females was significantly shorter than in the males. The systemic clearance (Cls) of antipyrine increased significantly between 1 and 18 months of age. No significant differences were observed between systemic clearance of antipyrine in males and females under 12 months. In 12 and 18 month-old animals the Cls values were significantly higher in females than in males. Following intravenous administration, recovery of antipyrine and its three main metabolites increased significantly with age. These values did not differ significantly between males and females under 12 month of age. In 12 and 18 month-old females the excretion of 4-OHA and HMA in urine was significantly higher than in males at the same age. The excretion of NORA and unchanged antipyrine in males and females did not differ significantly. The partial clearances of antipyrine metabolites (Cl(m)) increased significantly between 1 and 18 months of age. No significant differences were observed between Cl(m) values in males and females under 12 months of age. In 12 and 18 month-old females the partial clearances of 4-OHA and HMA were significantly higher than in males. The clearance of NORA was significantly higher in 18 month-old females than in males. In conclusion, we report a sex-linked difference in plasma antipyrine clearance and urinary excretion of the main metabolites of antipyrine in cattle over 12 months of age, the females being the more active metabolizers.     

Effects of guanidinoacetic acid on growth performance,creatine metabolism and plasma amino acid profile in broilers

The objective of this study was to assess the effects of guanidinoacetic acid (GAA) on growth performance, creatine deposition and blood amino acid (AA) profile on broiler chickens. In Exp. 1, a total of 540 one‐day‐old Arbor Acres male broilers (average initial body weight, 45.23 ± 0.35 g) were divided randomly into five treatments with six replicates of 18 chicks each. Broilers were fed corn–soybean meal‐basal diets supplemented with 0, 600, 800, 1,000 or 1,200 mg/kg GAA for 42 days respectively. Results showed that dietary GAA inclusion increased average daily gain (ADG) and improved gain‐to‐feed ratio (G:F) from 1 to 42 days (p < 0.01). However, average daily feed intake was unaffected by dietary supplementation of GAA. As GAA inclusion increased, the contents of creatine in plasma and kidney were increased (linear, p < 0.01), while the contents of GAA and creatine in liver were decreased (linear, p < 0.01). Similarly, GAA supplementation was inversely related to concentrations of most essential AA in plasma. In Exp. 2, a total of 432 one‐day‐old Arbor Acres male broilers (average initial body weight, 39.78 ± 0.58 g) were divided randomly into four treatments with six replicates of 18 chicks each. Birds were fed a corn–soybean meal‐basal diet supplemented with 0, 200, 400 or 600 mg/kg GAA for 42 days respectively. Dietary inclusion of 600 mg/kg GAA significantly increased ADG and G:F of broilers (p < 0.05). In conclusion, dietary supplementation of 600–1,200 mg/kg GAA can effectively improve the growth performance in broiler chickens by affecting creatine metabolism and utilization efficiency of essential AA, and 600 mg/kg GAA is the minimum dose for improving performance.     

Tolerance evaluation of overdosed dietary levels of 25‐hydroxyvitamin D3 in growing piglets

Forty‐eight, cross‐bred (GL × LW × P) piglets were used in a 42‐day tolerance trial to assess the effects of feeding diets supplemented with vitamin D or increasing levels of 25‐hydroxyvitamin D₃ (25‐OH‐D₃). Six‐week‐old piglets (24 castrate males, 24 females) were used. Two replicate groups of 6 piglets were randomized by weight and allocated to four dietary treatments. The control group (T1) was supplemented with 50 μg vitamin D₃/kg feed. The experimental groups received 25‐OH‐D₃ at the recommended dose (T2: 50 μg/kg = 1x), at 250 μg/kg (T3: 5x) or at 500 μg/kg (T4: 10x) respectively. Feed intake and daily weight gain were measured weekly, and the animals were examined by a veterinarian daily. After 42 days, body mass, blood, urine, bone and tissue samples were analysed and a pathology examination conducted. Dietary treatments had no significant effect on final body mass or daily weight gain. The 25‐OH‐D₃ plasma concentration in T1 was 17 ± 3 ng/ml (mean ± SD) while the respective values of the experimental groups were significantly increased in T2, T3 and T4. Tissue concentrations of 25‐OH‐D₃ were higher in liver and muscle for T3 and T4 and in skin for T4 than in T1. However, neither gross pathology nor histology, nor blood and urine characteristics, nor bone parameters were affected by dietary treatments. Weight of organs as well as dry matter, ash and calcium content of kidneys remained unaffected by dietary 25‐OH‐D₃ intake. Furthermore, no changes were observed for general indicators of health. The results of this study demonstrated that feeding piglets with 25‐OH‐D₃ at 5 or 10 times the recommended level had no adverse effects on any of the biological parameters measured. It was concluded that 25‐OH‐D₃ can be regarded as a supplement with a very high safety margin when used at the recommended level.     

Effects of rice feeding on growth performance and protein (amino acids) metabolism in weanling piglets

We investigated the effects of rice feeding on growth performance and protein (amino acids) metabolism of weanling piglets. In all, 16 weanling piglets with an average initial weight of 7.5 kg were divided into two groups. One group was fed a corn‐soybean meal‐based diet, and the other was fed a rice‐soybean meal diet, containing around 46% of corn or rice, respectively. A two‐week growth trial was conducted. The average daily gain (p = .025) and feed efficiency (p = .011) in rice‐fed piglets were significantly higher than those in corn‐fed piglets. Liver lysine‐ketoglutarate reductase activity tended to be lower (p = .073) in rice‐fed piglets than in corn‐fed piglets. Plasma urea nitrogen concentration in rice‐fed piglets was significantly lower than that in corn‐fed piglets. Plasma glucose and insulin concentrations were significantly higher in rice‐fed piglets than in corn‐fed piglets. Plasma‐free valine, isoleucine, and tryptophan concentrations were significantly higher in rice‐fed piglets than in corn‐fed piglets. In contrast, plasma histidine concentration was significantly lower in rice‐fed piglets than in corn‐fed piglets. Overall, these results show that rice feeding improves the growth performance and affects the protein (amino acids) metabolism in weanling piglets.