The influence of rapid growth on sodium salicylate pharmacokinetics in male turkeys

The aim of this study was to assess the influence of growth on the pharmacokinetics of sodium salicylate (SS) in male turkeys. SS was administered intravenously at a dose of 50 mg/kg. Plasma drug concentrations were assessed by high‐performance liquid chromatography, and pharmacokinetic parameters were calculated by noncompartmental analysis. As the age increased from 6 to 13 weeks (body weight increase from 2.35 to 9.43 kg), median body clearance decreased from 1.34 to 0.87 ml/min/kg. This caused a significant increase in the median mean residence time from 3.42 to 4.44 hr. Elimination phase proved to be biphasic and two elimination half‐lives (T_1/2el) were distinguished. Whereas T_1/2el1 was found to increase with age by 128%, T_1/2el2 represented a later but faster and less age‐dependent phase of elimination (increase by 56% in the respective groups). Volume of distribution decreased with age. These effects may lead to different therapeutic response to SS in turkeys of different age and body weights.     

Comparative pharmacokinetics of acetylsalicylic acid and sodium salicylate in chickens and turkeys

1. Pharmacokinetics of acetylsalicylic acid (ASA) and sodium salicylate (SS) were assessed following single intravenous (i.v.) and oral administration at doses of 50 mg/kg body weight to chickens and turkeys. Plasma drug concentrations were determined using high-performance liquid chromatography with ultraviolet detection and pharmacokinetic variables were calculated using a non-compartmental model.

2. The mean residence time (MRT) of salicylate (SA) after i.v. administration of SS was 6.08 ± 0.59 and 3.32 ± 0.27 h and after oral administration was 6.95 ± 0.72 and 4.55 ± 0.71 h in chickens and turkeys, respectively. The elimination half-life (T _{1/2 e}) was shorter in turkeys compared with chickens. The value of body clearance (Cl_B) was higher in turkeys than in chickens, but the apparent volume of distribution (V _ss) was similarly low in both species. The bioavailability of SS was complete and the maximal plasma concentration of SA (C _max) after oral administration was 96.93 ± 8.06 and 91.76 ± 9.64 µg/ml, respectively, in chickens and turkeys.

3. The MRT of ASA after iv administration was 0.24 ± 0.08 and 0.24 ± 0.02 h and after oral administration was 0.78 ± 0.25 and 0.59 ± 0.13 h, respectively, in chickens and turkeys. In both species, T _{1/2 e} was very short, Cl_B and V _ss were similar and markedly higher than those of salicylate. The bioavailability of unchanged ASA was low and C _max after oral administration was 6.9 ± 3.6 µg/ml in chickens and 8.6 ± 1.3 µg/ml in turkeys.     

Pharmacokinetics of Tilmicosin (Provitil Powder and Pulmotil Liquid AC) Oral Formulations in Chickens

A bioavailability and pharmacokinetics study of powder and liquid tilmicosin formulations was carried out in 18 healthy chickens according to a single-dose, two-period, two-sequence, crossover randomized design. The two formulations were Provitil and Pulmotil AC. Both drugs were administered to each chicken after an overnight fast on two treatment days separated by a 2-week washout period. A modified rapid and sensitive HPLC method was used for determination of tilmicosin concentrations in chicken plasma. Various pharmacokinetic parameters including area under plasma concentration–time curve (AUC₀₋₇₂), maximum plasma concentration (C _max), time to peak concentration (t _max), elimination half-life (t _1/2β), elimination rate (k _el), clearance (Cl_B), mean residence time (MRT) and volume of distribution (V _d,area) were determined for both formulations. The average means of AUC₀₋₇₂ for Provitil and Pulmotil AC were very close (24.24 ± 3.86, 21.82 ± 3.14 (μg.h)/ml, respectively), with no significant differences based on ANOVA. The relative bioavailability of Provitil as compared to Pulmotil AC was 111%. In addition, there were no significant differences in the C _max (2.09 ± 0.37, 2.12 ± 0.40 μg/ml), t _max (3.99 ± 0.84, 5.82 ± 1.04 h), t _1/2β (47.4 ± 9.32, 45.0 ± 5.73 h), k _el (0.021 ± 0.0037, 0.022 ± 0.0038 h⁻¹), Cl_B (19.73 ± 3.73, 21.37 ± 4.54 ml/(min/kg)), MRT (71.20 ± 12.87, 67.15 ± 9.01 h) and V _d,area (1024.8 ± 87.5, 1009.8 ± 79.5 ml/kg) between Pulmotil AC and Provitil, respectively. In conclusion, tilmicosin was rapidly absorbed and slowly eliminated after oral administration of single dose of tilmicosin aqueous and powder formulations. Provitil and Pulmotil AC can be used as interchangeable therapeutic agents.     

The pharmacokinetics of nitazoxanide active metabolite (tizoxanide) in goats and its protein binding ability in vitro

Zhao, Z., Xue, F., Zhang, L., Zhang, K., Fei, C., Zheng, W., Wang, X., Wang, M., Zhao, Z., Meng, X. The pharmacokinetics of nitazoxanide active metabolite (tizoxanide) in goats and its protein binding ability in vitro. J. vet. Pharmacol. Therap. 33 , 147–153. The pharmacokinetics of tizoxanide (T), the active metabolite of nitazoxanide (NTZ), and its protein binding ability in goat plasma and in the solutions of albumin and α‐1‐acid‐glycoprotein were investigated. The plasma and protein binding samples were analyzed using a high‐performance liquid chromatography (HPLC) assay with UV detection at 360 nm. The plasma concentration of T was detectable in goats up to 24 h. Plasma concentrations vs. time data of T after 200 mg/kg oral administration of NTZ in goats were adequately described by one‐compartment open model with first order absorption. As to free T, the values of t_1/2Ka, t_1/2Ke, T_max, C_max, AUC, V/F_(c), and Cl_(s) were 2.51 ± 0.41 h, 3.47 ± 0.32 h, 4.90 ± 0.13 h, 2.56 ± 0.25 μg/mL, 27.40 ± 1.54 (μg/mL) × h, 30.17 ± 2.17 L/kg, and 7.34 ± 1.21 L/(kg × h), respectively. After β‐glucuronidase hydrolysis to obtain total T, t_1/2ke, C_max, T_max, AUC increased, while the V/F_(c) and Cl_(s) decreased. Study of the protein binding ability showed that T with 4 μg/mL concentration in goat plasma and in the albumin solution achieved a protein binding percentage of more than 95%, while in the solution of α‐1‐acid‐glycoprotein, the percentage was only about 49%. This result suggested that T might have much more potent binding ability with albumin than with α‐1‐acid‐glycoprotein, resulting from its acidic property.     

Pharmacokinetic studies of levofloxacin after oral administration in healthy and febrile cow calves

The present experiment was designed to study the pharmacokinetics of levofloxacin in six healthy cross bred female cow calves (4 to 6 months age) weighing between 40 to 80 kg. Plasma from blood was separated by centrifugation at 10,000 rpm. Quantitative estimation of levofloxacin was done by UV-VIS spectrophotometer at 286 nm. The mean maximum plasma concentration (Cp_max ) of levofloxacin in febrile calves (5.28?±?0.32 µg/ml) did not differ significantly as compared with healthy calves (4.50?±?0.22 µg/ml) after single dose (20 mg/kg) oral administration. The mean therapeutic plasma concentration ( Cp_ther ) of levofloxacin was maintained for longer period in febrile calves (10 h) as compared to healthy calves ( 8 h). The mean maximum urine concentration (Cu_max) in febrile (40.86?±?2.19 µg/ml) also did not differ significantly as compared with healthy calves (39.38?±?2.43 µg/ml). No significant difference in various pharmacokinetic parameters of plasma was observed in healthy calves ( β?=?0.23?±?0.01/h ; t1/2 β?=?3.00?±?0.17 h and MRT?=?4.66?±?0.14 h ) and febrile calves ( β?=?0.23?±?0.01/ h; t1/2 β?=?3.05?±?0.16 h and MRT?=?5.04?±?0.14 h ) . The mean value of β, and t ½ β calculated in urine also did not differ between healthy and febrile calves. However, the value of MRT(3.79?±?0.07 h) and Cl_B(1.65?±?0.09 ml/kg/min) calculated in urine of febrile calves significantly(p?B?=?2.09?±?0.13 ml/kg/min). Based on kinetic profile levofloxacin may be given orally at the dose rate of 1.49 mg/kg B.W.at 8 h intervals in febrile calves.     

Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin in Male and Female Turkeys following Intravenous and Oral Administration

The pharmacokinetics of enrofloxacin (EFL) was investigated in turkeys (6 male and 6 female; 7-month-old at the start of the experiment), after intravenous and oral administration at a dose of 10 mg/kg body weight. The serum concentrations of EFL and its active metabolite ciprofloxacin (CFL) were determined by high-performance liquid chromatography. The serum concentrations vs time were analysed by a compartmental analysis. The mean values of EFL pharmacokinetic parameters showed differences only between values of V_d,ss (3.46±0.19 for the females and 4.53±0.11 L/kg for the males, p>0.05). The metabolite CFL was eliminated more slowly than its parent compound. There were no statistically significant differences between the values of the CFL pharmacokinetic parameters calculated for both sexes, excluding the higher values (p>0.05) of C_max in the females. The ratio AUC_CFL/AUC_EFL×100 was 4.4% in the male and 6.84% in the female birds. After oral administration of EFL the values of F(%) were 77.83 in the female and 79.61 in the male turkeys. Higher CFL serum concentrations were measured in females (p>0.05). The pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in turkeys can be characterized as similar to that in chickens and very similar between both sexes.     

Pharmacokinetics of gatifloxacin in broiler chickens following intravenous and oral administration

1. The pharmacokinetics of gatifloxacin were investigated following intravenous and oral administration of a single dose at a rate of 10?mg/kg body weight in broiler chicks.

2. Drug concentration in plasma was determined using High Performance Liquid Chromatography with ultraviolet detection on samples collected at frequent intervals after drug administration.

3. Following intravenous administration, the drug was rapidly distributed (t_1/2α: 0·33?±?0·008?h) and eliminated (t_1/2β: 3·62?±?0·03?h; Cl_B: 0·48?±?0·002?l/h/kg) from the body.

4. After oral administration, the drug was rapidly absorbed (C _max: 1·74?±?0·024?µg/mL; T _max: 2?h) and slowly eliminated (t_1/2β: 3·81?±?0·07?h) from the body. The apparent volume of distribution (V_d(area)), total body clearance (Cl_B) and mean residence time (MRT) were 3·61?±?0·04?l/kg, 0·66?±?0·01?l/h/kg and 7·16?±?0·08?h, respectively. The oral bioavailability of gatifloxacin was 72·96?±?1·10 %.

5. Oral administration of gatifloxacin at 10?mg/kg is likely to be highly efficacious against susceptible bacteria in broiler chickens.     

Pharmacokinetics of levofloxacin in Japanese quails (Coturnix japonica) following intravenous and oral administration

1. The pharmacokinetics of levofloxacin were investigated in Japanese quails after a single dose of 10?mg/kg BW, given either intravenously or orally.

2. Following intravenous administration, the mean value of distribution at steady state (Vd_ss), total body clearance (Cl_tot) and mean residence time (MRT) of levofloxacin were 1·25?l/kg, 0·39?l/h/kg and 2·72?h, respectively.

3. Following oral administration of levofloxacin, the peak plasma concentration (C_max) was 3·31?µg/ml and was achieved at a maximum time (T_max) of 2?h. Mean residence time (MRT), mean absorption time (MAT) and bioavailability were 4·26?h, 1·54?h and 69·01%, respectively. In vitro plasma protein binding of levofloxacin was 23·52%.

4. Based on pharmacokinetic and pharmacodynamic integration, an oral dose of 10?mg/kg levofloxacin for every 12?h is recommended for a successful clinical effect in quails.     

Effects of urine pH modification on pharmacokinetics of phenobarbital in healthy dogs

Although pH modification is one of the effective strategies for dissolving or preventing uroliths, little is known about its effects on the pharmacokinetics of phenobarbital in dogs. Five spayed, female Beagles were fed with a twice‐daily diet that included potassium citrate and ammonium chloride for urine alkalinization and acidification, respectively. After a stabilizing period of 7 days, a single clinical dose of phenobarbital (3 mg/kg) was orally administered, and time‐course changes in its serum and urine concentrations were determined by high‐performance liquid chromatography. Total amounts of unchanged phenobarbital excreted into urine for 216 h were decreased by urine acidification and increased by urine alkalinization. The elimination half‐life of serum phenobarbital in dogs with urine alkalinization was shortened and Cl_R increased when compared with dogs with urine acidification. Other pharmacokinetic parameters, including C_max, T_max, AUC_0–216, Cl/F, and A_e0–216 were not changed by modification of the urine pH. These results suggest that the pH of urine is likely to be a determinant of the pharmacokinetics, especially urine excretion rate, of a clinical dose of oral phenobarbital. It is possible that the serum concentration of phenobarbital might be altered when a pH modifying‐diet is administered for the purpose of dissolving or preventing uroliths.     

Effect of dietary supplementation with clay‐based binders on biochemical and histopathological changes in organs of turkey fed with aflatoxin‐contaminated diets

This study was carried out to investigate the effect of dietary supplementation with molecular or nano‐clay binders on biochemical and histopathological examination of organs of turkeys fed diets contaminated with aflatoxin B_1. Two hundred and sixteen unsexed 1‐day‐old British United Turkeys were randomly allotted to nine diets in a 3 × 3 factorial arrangement of diets supplemented with no toxin binder, molecular toxin binder (MTB) and nano‐clay toxin binder, each contaminated with 0, 60 and 110 ppb aflatoxin B₁ respectively. There were three replicates per treatment with eight turkeys per replicate. Biochemical analyses, organ weights and histopathological changes of some organs were examined at the end of the study which lasted for 84 days. Turkeys fed diets supplemented with molecular and nano‐binders showed higher (p < 0.001) total serum protein, reduced (p < 0.001) serum uric acid and GGT concentration values when compared with those fed aflatoxin‐contaminated diets supplemented with no binder. Turkeys fed aflatoxin‐contaminated diets supplemented with no binder had increased (p < 0.001) AST and ALT concentration when compared with other treatments. The heaviest (p < 0.001) liver and intestinal weight was noticed with turkeys fed diets supplemented with no binder and contaminated with 110 ppb aflatoxin B₁. Pathologically, there was no visible morphological alteration noticed in all turkeys fed uncontaminated diets and nano‐clay‐supplemented group. Hepatic paleness, hepatomegaly and yellowish discolouration of the liver were observed with turkeys fed diets containing no binder but contaminated with 60 and 110 ppb aflatoxin B1. Intestinal histopathological changes such as goblet cell hyperplasia, villous atrophy and diffuse lymphocytic enteritis were more prominent in turkeys fed diets containing no toxin binder and MTB. In conclusion, there were improved biochemical parameters and reduced deleterious effects of aflatoxin B₁ in turkeys fed diet supplemented with clay binders. However, the improvement was more conspicuous in the nano‐clay‐supplemented group than molecular clay group.     

Low ambient temperature elevates plasma triiodothyronine concentrations while reducing digesta mean retention time and methane yield in sheep

Ruminant methane yield (MY) is positively correlated with mean retention time (MRT) of digesta. The hormone triiodothyronine (T₃), which is negatively correlated with ambient temperature, is known to influence MRT. It was hypothesised that exposing sheep to low ambient temperatures would increase plasma T₃ concentration and decrease MRT of digesta within the rumen of sheep, resulting in a reduction of MY. To test this hypothesis, six Merino sheep were exposed to two different ambient temperatures (cold treatment, 9 ± 1 °C; warm control 26 ± 1 °C). The effects on MY, digesta MRT, plasma T₃ concentration, CO₂ production, DM intake, DM digestibility, change in body weight (BW), rumen volatile fatty acid (VFA) concentrations, estimated microbial protein output, protozoa abundance, wool growth, water intake, urine output and rectal temperature were studied. Cold treatment resulted in a reduction in MY (p < 0.01); digesta MRT in rumen (p < 0.01), hindgut (p = 0.01) and total digestive tract (p < 0.01); protozoa abundance (p < 0.05); and water intake (p < 0.001). Exposure to cold temperature increased plasma T₃ concentration (p < 0.05), CO₂ production (p = 0.01), total VFA concentrations (p = 0.03) and estimated microbial output from the rumen (p = 0.03). The rate of wool growth increased (p < 0.01) due to cold treatment, but DM intake, DM digestibility and BW change were not affected. The results suggest that exposure of sheep to cold ambient temperatures reduces digesta retention time in the gastrointestinal tract, leading to a reduction in enteric methane yield. Further research is warranted to determine whether T₃ could be used as an indirect selection tool for genetic selection of low enteric methane‐producing ruminants.     

Characterization of the pharmacokinetic disposition of levofloxacin in stallions after intravenous and intramuscular administration

The target of the present study was to investigate the plasma disposition kinetics of levofloxacin in stallions (n = 6) following a single intravenous (i.v.) bolus or intramuscular (i.m.) injection at a dose rate of 4 mg/kg bwt, using a two‐phase crossover design with 15 days as an interval period. Plasma samples were collected at appropriate times during a 48‐h administration interval, and were analyzed using a microbiological assay method. The plasma levofloxacin disposition was best fitted to a two‐compartment open model after i.v. dosing. The half‐lives of distribution and elimination were 0.21 ± 0.13 and 2.58 ± 0.51 h, respectively. The volume of distribution at steady‐state was 0.81 ± 0.26 L/kg, the total body clearance (Cl_tot) was 0.21 ± 0.18 L/h/kg, and the areas under the concentration–time curves (AUCs) were 18.79 ± 4.57 μg.h/mL. Following i.m. administration, the mean t_1/2el and AUC values were 2.94 ± 0.78 h and 17.21 ± 4.36 μg.h/mL. The bioavailability was high (91.76% ± 12.68%), with a peak plasma mean concentration (C_max) of 2.85 ± 0.89 μg/mL attained at 1.56 ± 0.71 h (T_max). The in vitro protein binding percentage was 27.84%. Calculation of efficacy predictors showed that levofloxacin might have a good therapeutic profile against Gram‐negative and Gram‐positive bacteria, with an MIC ≤ 0.1 μg/mL.     

Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin after Intramuscular Administration of Enrofloxacin in Goats

The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in goats after a single intramuscular administration of enrofloxacin at 2.5 mg/kg body weight. The plasma concentrations of enrofloxacin and ciprofloxacin were determined simultaneously by a HPLC method. The peak concentrations (C _max) of enrofloxacin (1.13 g/ml) and ciprofloxacin (0.24 g/ml) were observed at 0.8 and 1.2 h, respectively. The elimination half-life (t _1/2), volume of distribution (V _d(area)), total body clearance (Cl_B) and mean residence time (MRT) of enrofloxacin were 0.74 h, 1.42 L/kg, 1329 ml/h per kg and 1.54 h, respectively. The t _1/2, area under the plasma concentration–time curve (AUC) and the MRT of ciprofloxacin were 1.38 h, 0.74 g h/ml and 2.73 h, respectively. The metabolic conversion of enrofloxacin to ciprofloxacin was appreciable (36%) and the sum of the plasma concentrations of enrofloxacin and ciprofloxacin was maintained at or above 0.1 g/ml for up to 4 h. Enrofloxacin appears to be useful for the treatment of goat diseases associated with pathogens sensitive to this drug.     

Pharmacokinetics of sulphamethoxazole in calves and cows

Summary

The kinetics of sulphamethoxazole (SMZ) in plasma and milk, and its metabolism, protein binding and renal clearance were studied in three newborn calves and two dairy cows after intravenous administration. SMZ was predominantly acetylated; no hydroxy and glucuronide derivatives could be detected in plasma and urine. Age‐dependent pharmacokinetics and metabolism of SMZ were observed. The plasma concentration‐time curves of the N₄‐acetyl metabolite in the elimination phase were parallel to those of the parent drug; the N₄‐acetyl metabolite plasma percentage depended on age and ranged between 100% (new‐born) to 24.5% (cow). SMZ was rapidly eliminated (elimination half‐lives: 2.0–4.7 h) and exhibited a relatively small distribution volume (V_Darea: 0.44–0.57 l/kg). SMZ was excreted predominantly by glomerular filtration, while its N₄‐acetyl metabolite was actively eliminated by tubular secretion.     

The influence of age and body weight gain on enrofloxacin pharmacokinetics in turkeys—Allometric approach to dose optimization

Enrofloxacin is a concentration-dependent antimicrobial used in bacterial infections in poultry. During a few months of a turkey's life, pharmacokinetics of drugs undergoes substantial changes which may compromise their efficacy due to variability in internal exposure (measured by area under the concentration–time curve, AUC). The aim of this study was to describe the effects of age on the pharmacokinetics of a single intravenous (i.v.) and oral administration of enrofloxacin at a dose of 10 mg/kg to turkeys. It was found that during a 2.5-month-long period of growth from 1.4 to 14.6 kg, the AUC after i.v. administration increased almost threefold due to a significant decrease in the body clearance (from a mean of 0.76–0.28 L hr⁻¹ kg⁻¹). Over the same period, the mean elimination half-life was prolonged from 2.65 to 7.03 hr. Oral administration resulted in a similar trend in pharmacokinetic parameters. For both routes, formation of the major metabolite, ciprofloxacin, was marginal. Protein binding was not age-dependent and never exceeded 50%. Body clearance, volume of distribution and elimination half-life were subjected to an allometric analysis and a novel, nonlinear dosage protocol has been proposed to improve the internal exposure to the drug in different age groups of turkeys.     

Pharmacokinetics and cardiovascular effects following a single oral administration of a nonaqueous pimobendan solution in healthy dogs

Pimobendan is an inodilator used in the treatment of canine congestive heart failure (CHF). The aim of this study was to investigate the pharmacokinetics and cardiovascular effects of a nonaqueous oral solution of pimobendan using a single‐dose, operator‐blinded, parallel‐dose study design. Eight healthy dogs were divided into two treatment groups consisting of water (negative control) and pimobendan solution. Plasma samples and noninvasive measures of cardiovascular function were obtained over a 24‐h period following dosing. Pimobendan and its active metabolite were quantified using an ultra‐high‐performance liquid chromatography–mass spectrometer (UHPLC‐MS) assay. The oral pimobendan solution was rapidly absorbed [time taken to reach maximum concentration (T_max) 1.1 h] and readily converted to the active metabolite (metabolite T_max 1.3 h). The elimination half‐life was short for both pimobendan and its active metabolite (0.9 and 1.6 h, respectively). Maximal cardiovascular effects occurred at 2–4 h after a single oral dose, with measurable effects occurring primarily in echocardiographic indices of systolic function. Significant effects persisted for <8 h. The pimobendan nonaqueous oral solution was well tolerated by study dogs.     

Gene expression of endothelin-1 and its receptors in the heart of broiler chickens with T(3)-induced pulmonary hypertension

To investigate the effect of T₃-induced pulmonary hypertension on endothelin (ET) production and genes expression of ET-1, ET_A and ET_B receptors (ET_AR and ET_BR) during rearing, semiquantitative RT-PCR and enzyme immunometric assay were performed in the heart ventricles and serum, respectively. The ET-1 and its receptor genes were expressed in the right and left ventricles of control and T₃-treated broilers at 12, 28 and 49 days of age. There were significant (P < 0.05) reductions of the relative amounts of ET-1 (in both ventricles) and ET_AR (in the right ventricle) mRNAs at 28 and 49 days of age, in T₃-treated broilers compared to controls. The relative amounts of ET_BR mRNA in the right and left ventricles did not significantly differ between control and T₃-treated broilers at any age. The serum level of ET was significantly (P < 0.05) increased in T₃-treated chickens at 28 and 49 days of age when compared with that of the control. It is concluded that ET-1, ET_AR and ET_BR genes are normally expressed in the heart ventricles of broilers. It is likely that increased serum level of ET and decreased ET-1/ET_AR genes expression in the ventricles are involved in the heart dysfunction of broiler chickens with developmental pulmonary hypertension.     

Effects of dietary calcium content and vitamin D source on skeletal properties in growing turkeys

1. The aim of the study was to investigate the effects of feeding fast growing turkeys with differentiated dietary calcium (Ca) content, and the partial replacement of vitamin D₃ in the feed with 25-hydroxycholecalciferol (25(OH)D₃), on skeletal properties.

2. One-day-old Big-6 male turkeys (n?=?1008) were randomly divided into 4 groups, and two subgroups were created within each group. The groups were differentiated with 4 levels of Ca provision in the feed, namely 85% of the National Research Council (NRC) recommendation (Group Ca₁); 95% as above (Group Ca₂); 105% as above (Group Ca₃); and 115% as above (Group Ca₄). The first subgroup received the recommended dosage of cholecalciferol (vitamin D₃ subgroup) in the feed, while in the second subgroup (Hy-D subgroup), half of the dosage of cholecalciferol was replaced with 25(OH)D₃. At the ages of 4, 8, 12 and 20 weeks, 7 turkeys from each subgroup were randomly selected and killed to obtain the right tibia for densitometric, geometric and mechanical analyses.

3. This study showed advantageous effects of increased calcium supply in the diet on skeletal system properties, that were increased and produced the most desirable traits in turkeys receiving 95%, 105% and 115% of the NRC calcium recommendation. Benefits resulting from administration of 25(OH)D₃ in the diet were also obtained in the skeletal formation of turkeys, and the most advantageous effects were present in the group receiving 105% of recommended dietary Ca.

4. Effects on the metabolic response of the skeleton of turkeys to manipulation of dietary calcium content and vitamin D₃ source were the most evident in the groups between 4 and 12 weeks of life, and demonstrated a limited ability to induce a positive influence on bone properties at advanced stages of the production cycle by alteration of these dietary factors.