Relative Bioavailability Values Research Articles

Synthesis, Characterization, and Bioavailability in Rats of Ferric Phosphate Nanoparticles

Particle size is a determinant of iron (Fe) absorption from poorly soluble Fe compounds. Decreasing the particle size of metallic Fe and ferric pyrophosphate added to foods increases Fe absorption. The aim of this study was to develop and characterize nanoparticles of FePO4 and determine their bioavailability and potential toxicity in rats. Amorphous FePO4 nanopowders with spherical structure were synthesized by flame spray pyrolysis (FSP). The nanopowders were characterized and compared with commercially available FePO4 and FeSO4, including measurements of specific surface area (SSA), structure by transmission electron microscopy, in vitro solubility at pH 1 and 2, and relative bioavailability value (RBV) to FeSO4 in rats using the hemoglobin repletion method. In the latter, the potential toxicity after Fe repletion was assessed by histological examination and measurement of thiobarbituric acid reactive substances (TBARS). The commercial FePO4 and the 2 FePO4 produced by FSP (mean particle sizes, 30.5 and 10.7 nm) had the following characteristics: SSA: 32.6, 68.6, 194.7 m2/g; in vitro solubility after 30 min at pH 1: 73, 79, and 85% of FeSO4; and RBV: 61, 70, and 96%, respectively. In the histological examinations and TBARS analysis, there were no indications of toxicity. In conclusion, nanoparticles of FePO4 have a solubility and RBV not significantly different from FeSO4. Reducing poorly soluble Fe compounds to nanoscale may increase their value for human nutrition.

Physicochemical properties and bioavailability of five sources of ferric orthophosphate in ready‐to‐eat cereal

The light color and oxidative stability of ferric orthophosphate (FeOP4) make it an attractive iron fortificant. However, FeOP4 has had limited use in cereal due its variable source-to-source bioavailability. An understanding of the mechanisms underlying this variability may facilitate production of a FeOP4 source with consistent bioavailability. Five FeOP4 sources were processed into ready-to-eat cereal, added to diets, and fed to anemic rats for 2-wks. The relative bioavailability values (RBVs) ranged from 51 – 99% (see table). Sources 1–3 were standard Fe2So4, RBV=100, and 2 controls (not presented). Particle surface area (SA) and mean particle size (MPS) influence solubility. SA, PS, and the PS distribution may partially explain the variable RBVs (see table). Preferential moisture uptake by the amorphous content of the samples, measured by Dynamic Vapor Sorption, provides further explanation (see table). In summary, the variable RBV of FeOP4 appears to be influenced by a combination of SA, PS, and amorphous content. Funded by the Kellogg Company. Ferric Orthophosphate Characteristics

Comparative Bioavailability of Norfloxacin Tablets Based on Blood and Urine Data

Objective: To assess the bioavailability of norfloxacin from urinary excretion relative to plasma concentration. Materials and Methods: Twelve healthy volunteers (22–33 years) participated in the study. Each received a previously developed (M), a local (L) and a multinational (Noroxin®) tablet (Ref), 400 mg each, according to a random balanced three-way crossover design on 3 different days. Blood samples were collected over a 12-hour period and urine over a 24-hour period. Norfloxacin concentrations were analyzed by a validated HPLC method. Results: An initial estimate of bioequivalence of the three products was obtained using analysis of variance on transformed data and based on confidence interval calculation. Elimination pharmacokinetic parameters (half-life and renal clearance) calculated from plasma concentration and urinary excretion data (mean values, n = 36) were comparable to reported values for norfloxacin. Interproduct differences in elimination parameters (mean values, n = 12) were statistically insignificant (F values, ANOVA). Strong association was found between the mean of plasma concentration and urinary excretion rates for many volunteers (F values, regression analysis). Relative bioavailability values calculated for the local and previously developed products relative to Noroxin were higher than 85% based on area under the curve and urinary excretion. Bioequivalence could not be established among the three tested products based on calculated 90% confidence intervals. Conclusion: Urinary excretion of norfloxacin may be a useful noninvasive tool for bioavailability assessment of norfloxacin oral formulations.

Bioaccessibility of Carotenoids and Vitamin E from Their Main Dietary Sources

Vitamin E and carotenoids are fat-soluble microconstituents that may exert beneficial effects in humans, including protection against cancer, cardiovascular diseases, and age-related eye diseases. Their bioavailability is influenced by various factors including food matrix, formulation, and food processing. Since human studies are labor-intensive, time-consuming, and expensive, the in vitro model used in this study is increasingly being used to estimate bioaccessibility of these microconstituents. However, the ability of this model to predict bioavailability in a healthy human population has not yet been verified. The first aim of this study was to validate this model by comparing model-derived bioaccessibility data with (i) human-derived bioaccessibility data and (ii) published mean bioavailability data reported in studies involving healthy humans. The second aim was to use it to measure alpha- and gamma-tocopherol, beta-carotene, lycopene, and lutein bioaccessibility from their main dietary sources. Bioaccessibility as assessed with the in vitro model was well correlated with human-derived bioaccessibility values (r = 0.90, p < 0.05), as well as relative mean bioavailability values reported in healthy human groups (r = 0.98, p < 0.001). The bioaccessibility of carotenoids and vitamin E from the main dietary sources was highly variable, ranging from less than 0.1% (beta-carotene from raw tomato) to almost 100% (alpha-tocopherol from white bread). Bioaccessibility was dependent on (i) microconstituent species (lutein > beta-carotene and alpha-carotene > lycopene and alpha-tocopherol generally > gamma-tocopherol), (ii) food matrix, and (iii) food processing.

Pharmacokinetic interaction between fluvastatin and diltiazem in rats

The present study aimed to investigate the effect of fluvastatin on the pharmacokinetics of diltiazem in rats. Pharmacokinetic parameters of diltiazem were determined in rats following an oral administration of diltiazem (15 mg/kg) in the presence and absence of fluvastatin (0.6 and 2.0 mg/kg). Compared with the control given diltiazem alone, the C(max) and AUC of diltiazem increased by 30-70% in rats with the concurrent use of fluvastatin, while there was no significant change in T(max) and the plasma half-life (T(1/2)) of diltiazem. Consequently, absolute and relative bioavailability values of diltiazem in the presence of fluvastatin were significantly higher (p<0.05) than those from the control group, implying that fluvastatin could reduce the presystemic extraction of diltiazem. In conclusion, the concurrent use of fluvastatin significantly enhanced the oral exposure of diltiazem in rats.

Population Pharmacokinetics of Atazanavir in Patients with Human Immunodeficiency Virus Infection

Atazanavir (ATV) is a new azapeptide protease inhibitor recently approved and currently used at a fixed dose of either 300 mg once per day (q.d.) in combination with 100 mg ritonavir (RTV) or 400 mg q.d. without boosting. ATV is highly bound to plasma proteins and extensively metabolized by CYP3A4. Since ATV plasma levels are highly variable and seem to be correlated with both viral response and toxicity, dosage individualization based on plasma concentration monitoring might be indicated. This study aimed to assess the ATV pharmacokinetic profile in a target population of HIV patients, to characterize interpatient and intrapatient variability, and to identify covariates that might influence ATV disposition. A population analysis was performed with NONMEM with 574 plasma samples from a cohort of 214 randomly selected patients receiving ATV. A total of 346 randomly collected ATV plasma levels and 19 full concentration-time profiles at steady state were available. The pharmacokinetic parameter estimates were an oral clearance (CL) of 12.9 liters/h (coefficient of variation [CV], 26%), a volume of distribution of 88.3 liters (CV, 29%), an absorption rate constant of 0.405 h(-1) (CV, 122%), and a lag time of 0.88 h. A relative bioavailability value was introduced to account for undercompliance due to infrequent follow-ups (0.81; CV, 45%). Among the covariates tested, only RTV significantly reduced CL by 46%, thereby increasing the ATV elimination half-life from 4.6 h to 8.8 h. The pharmacokinetic parameters of ATV were adequately described by a one-compartment population model. The concomitant use of RTV improved the pharmacokinetic profile. However, the remaining high interpatient variability suggests the possibility of an impact of unmeasured covariates, such as genetic traits or environmental influences. This population pharmacokinetic model, together with therapeutic drug monitoring and Bayesian dosage adaptation, can be helpful in the selection and adaptation of ATV doses.

Altered pharmacokinetics of paclitaxel by the concomitant use of morin in rats

The purpose of this study was to investigate the effect of morin on the pharmacokinetics of orally and intravenously administered paclitaxel in rats. Pharmacokinetic parameters of paclitaxel were determined in rats after an oral (30 mg kg −1) or intravenous (3 mg kg −1) administration of paclitaxel to rats in the presence and absence of morin (3.3 and 10 mg kg −1). Compared to the control given paclitaxel alone, pretreatment with morin 30 min prior to the oral administration of paclitaxel increased C max and AUC of paclitaxel by 70–90% and 30–70%, respectively, while there was no significant change in T max and terminal plasma half-life ( T 1/2) of paclitaxel. Consequently, absolute and relative bioavailability values of paclitaxel in the rats after the pretreatment with morin were significantly higher ( p < 0.05) than those from the control. In contrast, following an intravenous administration of paclitaxel (3.3 mg kg −1), the pharmacokinetic profiles of paclitaxel were not altered significantly in the presence of morin. Those results suggest that the enhanced oral exposure of paclitaxel should be mainly due to the inhibition effect of morin on the gastrointestinal extraction of paclitaxel during the intestinal absorption. Therefore, the concurrent use of morin or morin-containing dietary supplement may provide a therapeutic benefit in the oral delivery of paclitaxel.

Comparative Species Utilization and Toxicity of Sulfur Amino Acids

Animal studies have shown that several methionine (Met) and cysteine (Cys) analogs or precursors have L-Met- and L-Cys-sparing activity. Relative oral bioavailability (RBV) values, with the L-isomer of Met and Cys set at 100% (isosulfurous basis), are near 100% for D-Met for animals but only about 30% for humans. Both the OH and keto analogs of Met have high RBV-sparing values, as does N-acetyl-L-Met (the D-isomer of acetylated Met has no bioactivity). L-Homocysteine has an RBV value of about 65% for Met sparing in rats and chicks, but D-homocysteine has little if any Met-sparing activity. S-Methyl-L-Met can partially spare Met, but only when fed under dietary conditions of choline/betaine deficiency. Relative to L-Cys, high RBV values exist for L-cystine, N-acetyl-L-Cys, L-homocysteine, L-Met, and glutathione, but D-cystine, the keto analog of Cys, L-cysteic acid, and taurine have no Cys-sparing activity. l-2-Oxothiazolidine-4-carboxylate has an RBV value of 75%, D-homocysteine 70%, and DL-lanthionine 35% as Cys precursors. Under dietary conditions of Cys deficiency and very low inorganic sulfate (SO4) ingestion, dietary SO4 supplementation has been shown to reduce the Cys requirement of several animal species as well as humans. Excessive ingestion of Met, Cys, or cystine has also been studied extensively in experimental animals, and these sulfur amino acids (SAA) are well established as being among the most toxic of all amino acids that have been studied. Even though Cys and its oxidized product (cystine) are equally efficacious at levels at or below their dietary requirements for maximal growth, Cys is far more toxic than cystine when administered orally in the pharmacologic dosing range. Isosulfurous (excess) levels of cystine, N-acetyl-L-Cys, or glutathione are far less growth depressing than L-Cys when 6 to 10 times the minimally required level of these SAA compounds are fed to chicks.

Estimation of Relative Bioavailability of Lead in Soil and Soil-Like MaterialsUsing Young Swine

In this article we summarize the results of a series of studies that measured the relative bioavailability (RBA) of lead in a variety of soil and soil-like test materials. Reference material (Pb acetate) or Pb-contaminated soils were administered orally to juvenile swine twice a day for 15 days. Blood samples were collected from each animal at multiple times during the course of the study, and samples of liver, kidney, and bone were collected at sacrifice. All samples were analyzed for Pb. We estimated the RBA of a test material by fitting mathematical models to the dose–response curves for each measurement end point and finding the ratio of doses that gave equal responses. The final RBA for a test material is the simple average of the four end point–specific RBA values. Results from 19 different test materials reveal a wide range of RBA values across different exposure materials, ranging from 6 to 105%. This variability in RBA between different samples highlights the importance of reliable RBA data to help improve risk assessments for Pb in soil. Although the RBA value for a sample depends on the relative amounts of the different chemical and physical forms of Pb present, data are not yet adequate to allow reliable quantitative predictions of RBA from chemical speciation data alone.

Iron status and food matrix strongly affect the relative bioavailability of ferric pyrophosphate in humans

Although ferric pyrophosphate is a promising compound for iron fortification of foods, few data are available on the effect of food matrices, processing, and ascorbic acid on its bioavailability. We compared the relative bioavailability (RBV) of ferrous sulfate in an experimental form of micronized dispersible ferric pyrophosphate (MDFP) in a wheat-milk infant cereal given with and without ascorbic acid with the RBV of MDFP from a processed and unprocessed rice meal. A crossover design was used to measure iron absorption in young women (n = 26) from test meals fortified with isotopically labeled [57Fe]-MDFP and [58Fe]-ferrous sulfate, based on erythrocyte incorporation of stable isotope labels 14 d later. Geometric mean iron absorption from the wheat-based meal fortified with MDFP was 2.0% and that from the meal fortified with ferrous sulfate was 3.2% (RBV = 62). The addition of ascorbic acid at a molar ratio of 4:1 to iron increased iron absorption from MDFP to 5.8% and that from ferrous sulfate to 14.8% (RBV = 39). In the rice meals, mean iron absorption from MDFP added to the rice at the time of feeding was 1.7%, and that from ferrous sulfate was 11.6% (RBV = 15). The mean iron absorption from MDFP extruded into artificial rice grains was 3.0% and that from ferrous sulfate in unprocessed rice was 12.6% (RBV = 24). Sixteen of 26 subjects were iron deficient. Iron status was a highly significant predictor of the RBV of MDFP (P < 0.001). RBV of the experimental MDFP varied markedly with food matrix and iron status. Assigning a single RBV value to poorly soluble compounds may be of limited value in evaluating their suitability for food fortification.

Enhanced oral exposure of diltiazem by the concomitant use of naringin in rats

The present study aims to investigate the effect of naringin, a flavonoid, on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined in rats following an oral administration of diltiazem (15 mg kg −1) to rats in the presence and absence of naringin (5 and 15 mg kg −1). Compared to the control given diltiazem alone, the C max and AUC of diltiazem increased by twofolds in rats pretreated with naringin, while there was no significant change in T max and terminal plasma half-life ( T 1/2) of diltiazem. Consequently, absolute and relative bioavailability values of diltiazem in the presence of naringin were significantly higher ( p < 0.05) than those from the control group. Metabolite–parent AUC ratio in the presence of naringin decreased by 30% compared to the control group, implying that naringin could be effective to inhibit the metabolism of diltiazem. In conclusion, the concomitant use of naringin significantly enhanced the oral exposure of diltiazem in rats.

Relative bioavailability of zinc in supplemental inorganic and organic sources for Nile tilapia Oreochromis niloticus fingerlings

A 90-day feeding experiment was conducted with sex reversed Nile tilapia (Oreochromis niloticus) fingerlings fed purified or practical diets supplemented with different zinc sources to evaluate fish growth performance and zinc and iron retention in fish bones, fillets, liver, skin and eyes. The relative bioavailability value (RBV) of zinc in the supplemental sources tested was also calculated. Fish were fed with isonitrogenous and isoenergetic purified or practical diets supplemented with 150 mg Zn kg−1, as zinc sulphate monohydrate (ZnSO4), zinc oxide (ZnO) or zinc amino acid complex (Zn-AA). The feeding trial was conducted in 30, 50 L aquaria where four 0.66 ± 0.01 g (mean ± SD) fingerlings were initially stocked. No significant differences were observed for any growth performance variables (P > 0.05). In practical diets, only ZnSO4 and ZnO presented bone zinc retention similar to that for the standard zinc source. Zinc concentration in the bone of fish fed practical diet supplemented with Zn-AA (171 ± 3.62 μg g−1) was significantly lower than that verified for the practical diets supplemented with the standard zinc source (200 ± 17.7 μg g−1) or with ZnSO4 (204 ± 19.9 μg g−1). Assuming the concentration of zinc in bones as the response criterion, the supplemental zinc RBV from ZnSO4 (105%) was higher than the RBV for Zn-AA (95.1%) or ZnO (94.9%). Iron concentration in the bones of animals fed the non-zinc-supplemented purified diet was significantly higher than that observed for purified diet supplemented with Zn-AA (P < 0,05). The results of the present work allowed us to conclude that ZnSO4 in relation to ZnO or Zn-AA was the supplemental zinc source with higher zinc bioavailability to Nile tilapia.

Pharmacokinetic interaction between diltiazem and morin, a flavonoid, in rats

The present study aims to investigate the effect of morin, a flavonoid, on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined in rats after an oral administration of diltiazem (15 mg kg −1) to rats in the presence and absence of morin (1.5, 7.5 and 15 mg kg −1). Compared to the control given diltiazem alone, the C max and AUC of diltiazem increased by 30–120% in the rats co-administered with a 1.5 or 7.5 mg kg −1 of morin, while there was no significant change in T max and terminal plasma half-life ( T 1/2) of diltiazem in the presence of morin. Consequently, absolute and relative bioavailability values of diltiazem in the rats co-administered with morin were significantly higher ( p < 0.05) than those from the control group. Metabolite-parent AUC ratio in the presence of morin (7.5 mg kg −1) decreased by 30% compared to the control group, implying that coadministration of morin could be effective to inhibit the CYP3A4-mediated metabolism of diltiazem. In conclusion, the presence of morin significantly enhanced the oral exposure of diltiazem, suggesting that concurrent use of morin or morin-containing dietary supplement with diltiazem should require close monitoring for potential drug interactions.

Nasal insulin delivery in the chitosan solution: in vitro and in vivo studies

The effects of chitosan concentrations, osmolarity, medium and absorption enhancers in the chitosan solution on nasal insulin delivery were studied in vitro and in vivo. The penetration of insulin through the mucosa of rabbit nasal septum was investigated by measuring the transmucosal flux in vitro, while the nasal absorption of insulin in vivo was assessed by the efficiency in lowering the blood glucose levels in normal rats. It was demonstrated that increasing concentrations of chitosan up to 1.5% (w/v) caused an increase in the permeability of insulin across the nasal mucosa. Insulin given intranasally in hypo- or hyperosmotic formulation showed a higher hypoglycemic effect than insulin delivered in isoosmotic formulation. Insulin formulation in chitosan solution prepared with deionized water brought to a higher relative pharmacological bioavailability (Fr) value than that prepared with 50 mM pH 7.4 phosphate buffer. A formulation containing both 1% chitosan and 0.1% ethylenediaminetetraacetic acid (EDTA), 5% polysorbate 80 (Tween 80) or 1.2% β-cyclodextrin (β-CD) did not lead to a higher Fr than insulin formulated with 1% chitosan alone. The formulation containing both 5% hydroxypropyl-β-cyclodextrin (HP-β-CD) and 1% chitosan was more effective at reducing blood glucose levels than the formulation containing 5% HP-β-CD or 1% chitosan alone. The studies indicated that chitosan concentrations, osmolarity, medium and absorption enhancers in chitosan solution have significant effect on the insulin nasal delivery. The results of in vitro experiments were in good agreement with that of in vivo studies.

Effect of Ascorbic Acid and Particle Size on Iron Absorption from Ferric Pyrophosphate in Adult Women

The effects of added ascorbic acid and particle size on iron absorption from ferric pyrophosphate were evaluated in adult women (9-10 women/study) based on erythrocyte incorporation of iron stable isotopes (57Fe or 58Fe) 14 days after administration. Three separate studies were made with test meals of iron-fortified infant cereal (5 mg iron/meal) and the results are presented as geometric means and relative bioavailability values (RBV, FeSO4 = 100%). The results of study 1 showed that iron absorption was significantly lower from ferric pyrophosphate (mean particle size 8.5 microm) than from FeSO4 in meals without ascorbic acid (0.9 vs. 2.6%, p < 0.0001, RBV 36%) and in the same meals with ascorbic acid added at a 4:1 molar ratio relative to fortification iron (2.3 vs. 9.7%, p < 0.0001, RBV 23%). Ascorbic acid increased iron absorption from ferric pyrophosphate slightly less (2.6-fold) than from FeSO4 (3.7-fold) (p < 0.05). In studies 2 and 3, RBV of ferric pyrophosphate with an average particle size of 6.7 microm and 12.5 pm was not significantly different at 52 and 42% (p > 0.05), respectively. In conclusion, the addition of ascorbic acid increased fractional iron absorption from ferric pyrophosphate significantly, but to a lesser extent than from FeSO4. Decreasing the mean particle size to 6.7 microm did not significantly increase iron absorption from ferric pyrophosphate.

Relative Bioavailability of Novel Amino Acid Chelates of Manganese and Copper for Chicks

ABSTRACT Two experiments were conducted to estimate the relative bioavailability of two new organic chelates of Mn or Cu compared with either reagent-grade Mn sulfate monohydrate or reagentgrade Cu sulfate pentahydrate as the standards in chicks fed for 21 d. Based on either bone Mn concentration, regressed on added dietary Mn concentration, or log10 liver Cu concentration, regressed on non-zero added dietary Cu intake, and assuming a value of 100% for either reagentgrade standard, relative bioavailability values were 84 ± 3.5 and 96 ± 14%, for the Mn and Cu chelates, respectively.

Enhanced bioavailability of piroxicam using Gelucire 44/14 and Labrasol: in vitro and in vivo evaluation

Piroxicam is a non-steroidal anti-inflammatory drug that is characterized by low solubility and high permeability. The purpose of the study was to investigate the in vitro and in vivo performance of the semi-solid dispersion prepared with Gelucire 44/14 and Labrasol into hard gelatin capsules (GL) for enhancing the dissolution rate of the drug. The results were evaluated by comparing with pure piroxicam filled into hard gelatin capsules (PP) and a commercially available tablet dosage form containing a piroxicam:β-cyclodextrin complex (CD). The in vitro dissolution testing of the dosage forms was performed in different media (simulated gastric fluid, pH 1.2; phosphate buffers, pH 4.5 and 6.8; and water). Amongst the dosage forms, GL provided at least 85% piroxicam dissolution within 30 min in each of the media, behaving like a fast-dissolving immediate release drug product. Oral bioavailability of 20 mg piroxicam in GL, CD, and PP was compared after administration of a single dose to eight healthy volunteers. Three treatments were administered in crossover fashion, separated by a washout period of 2 weeks. Piroxicam was monitored in plasma by high-performance liquid chromatography. The apparent rate of absorption of piroxicam from GL ( C max=2.64 μg/ml, t max=82.5 min) was significantly higher than that of the PP ( C max=0.999 μg/ml, t max=144 min) ( P<0.05) and similar to that of CD ( C max=2.44 μg/ml, t max=120 min) ( P>0.05). The relative bioavailability values as the ratios of mean total AUC for GL relative to PP and CD, were 221 and 98.6%. Piroxicam is characterized by a slow and gradual absorption via the oral route and this causes a delayed onset of therapeutic effect. Thus, plain piroxicam preparations are not indicated for analgesia. The results of the in vivo study revealed that the GL dosage form would be advantageous with regards to rapid onset of action, especially in various painful conditions where an acute analgesic effect is desired.

Relative bioavailability of organic zinc sources based on tissue zinc and metallothionein in chicks fed conventional dietary zinc concentrations

An experiment was conducted to estimate relative bioavailability (RBV) of Zn in Zinc proteinate and Zinc methionine compared to Zinc acetate as the standard. A total of 432, 1-day-old male broiler chicks was assigned randomly to dietary treatments which included the basal maize–soyabean meal diet (24 mg Zn kg −1 DM) supplemented with 0, 30, 60, or 90 mg kg −1 added Zn as reagent grade Zinc acetate or 30 or 60 mg kg −1 added Zn from Zinc methionine or Zinc proteinate fed for 3, 6, or 9 days. Accumulation of Zn in bone increased ( P<0.001) with supplemental Zn and age. Bone Zn concentration was greater ( P<0.001) in chicks given Zinc proteinate. Hepatic and mucosal metallothionein (MT) increased ( P<0.001) with supplemented Zn and age. Using Zinc acetate as a standard (1.00) in multiple linear regressions gave estimated RBV values of 1.10, 1.24, and 1.16 for Zinc proteinate and 0.88, 0.91 and 0.78 for Zinc methionine at 3, 6, and 9 days, respectively, based on bone Zn concentrations. Similar estimates were calculated using mucosal MT. The coefficient of determination was greater for the mucosal MT regression at 3 days compared to that for bone Zn. Mucosal MT appears to be a suitable criterion to estimate bioavailability of Zn sources during short term trials.

Zinc Bioavailability in Tetrabasic Zinc Chloride and the Dietary Zinc Requirement of Young ChicksFed a Soy Concentrate Diet

Three chick assays were conducted to determine a bioavailable Zn requirement and to establish a Zn relative bioavailability (RBV) value for tetrabasic Zn chloride [TBZC, i.e., Zn5Cl2(OH)8]. In Assay 1, 8-d-old chicks were fed a Zn-deficient soy concentrate diet (8.8 mg/kg bioavailable Zn) supplemented with 0, 5.81, 10.81, 15.10, and 20.25 mg Zn/kg from ZnSO4.7H2O for 14 d to establish a linear response range and estimate a bioavailable Zn requirement. Weight gain of chicks increased linearly (P < 0.01; r2 = 0.99) when the first three levels of Zn were fed. Broken-line analysis of the weight gain data indicated a bioavailable Zn requirement of 22.4 mg/kg. In Assay 2, RBV of Zn in TBZC was determined by multiple-linear regression slope-ratio methodology. The Zn-deficient basal diet was supplemented with 0, 5.81, and 10.81 mg Zn/kg from ZnSO4.7H2O to produce a linear growth response as determined in Assay 1. The same basal diet was supplemented with 5.38 and 10.81 mg Zn/kg from TBZC. The RBV of Zn in TBZC was found to be 102%, which was not different (P > 0.10) from 100%. A third assay was conducted as described for Assay 2, and the RBV of Zn in TBZC was 111%, which was not different from 100%. In summary, the RBV of Zn in TBZC was not different from that of ZnSO4.7H2O, and the minimal bioavailable Zn requirement for chicks 1 to 3 wk of age fed a soy concentrate diet was estimated at 22.4 mg/kg.

Chemical characteristics and relative bioavailability of supplemental organic copper sources for poultry.

Five commercially available organic Cu products and reagent-grade CuSO4 x 5H2O (Cu Sulf) were evaluated by polarographic analysis and solubility in 0.1 M K2HPO4-KH2PO4 buffer (pH 5), 0.2 M HCl-KCl buffer (pH 2), or deionized water. Fractions from these solubility tests were evaluated by gel filtration chromatography for structural integrity. The organic sources were Cu lysine complex (Cu Lys), Cu amino acid chelate (Cu AA), Cu proteinate A (Cu ProA), Cu proteinate B (Cu ProB), and Cu proteinate C (Cu ProC). Separation of peaks in the chromatograms for the soluble Cu fraction from deionized water indicated that 77, 31, 69, 94, and 16% of the Cu remained chelated for the above sources, respectively. Two experiments were conducted to estimate the relative bioavailability of Cu from the organic Cu supplements for chicks when added at high dietary concentrations to practical corn-soybean meal diets. Liver Cu concentration increased (P < 0.0001) as dietary Cu increased in both experiments. When Cu Sulf was assigned a value of 100% as the standard, linear regression slope ratios of log10 liver Cu concentration regressed on added dietary Cu concentration gave estimated relative bioavailability values of 124 +/- 5.1, 122 +/- 5.3, and 111 +/- 6.0 for Cu Lys, Cu AA, and Cu ProC, respectively, in Exp. 1. The bioavailability estimates for Cu Lys and Cu AA were greater (P < 0.05) than that for Cu Sulf. Values in Exp. 2 were 111 +/- 7.6, 109 +/- 8.4, and 105 +/- 7.5 for Cu Lys, Cu ProA, and Cu ProB, respectively, and all sources were similar in value for chicks. Solubility of Cu in pH 2 buffer provided the best prediction of bioavailability (r2 = 0.924). Other indicators of chelation integrity and solubility had little value as predictors of bioavailability (r2 < or = 0.445).