Relative Bioavailability Values Research Articles

Source and bioavailability of quaternary ammonium compounds (QACs) in dust: Implications for Nationwide Exposure in China

Quaternary ammonium compounds (QACs), widely used in various disinfectants products during the COVID-19 Pandemic, raised the concerns on their exposure and health effect. To date, the sources of QACs in indoor environments have been largely ignored. Additionally, there is no information on the nationwide human exposure assessment of QACs in China after the COVID-19. Herein, analysis of QACs in household products, including personal care (n = 27), cleaning (n = 6) and disinfection products (n = 11) from different manufacturing companies further confirmed there are extensive application of QACs in household products, raising their potential exposure to humans. QACs were frequently detected in indoor dust samples (n = 370) from 111 cities of 31 provinces/municipalities across China, with median concentration of 6778 ng/g. Benzalkyldimethylammonium compounds (BACs) and alkyltrimethylammonium compounds (ATMACs) were identified as the dominant QACs in dust samples, with the proportions of 44 % and 46 %, respectively. The in vivo bioavailability experiment (C57BL/6 male mice) showed that the relative bioavailability (RBA) of QACs through dust ingestion ranged from 5.08 % to 66.3 % and 60.3 % to 118 % in the low and high-dose group, respectively. Compared to the pre-adjustment scenario of RBA values, the exposure risk of QACs was overestimated by 2.23 – 5.14 times.

Design and Evaluation of Clove Oil-Based Self-Emulsifying Drug Delivery Systems for Improving the Oral Bioavailability of Neratinib Maleate.

Neratinib maleate (NM), a tyrosine kinase inhibitor, is used in the treatment of breast cancer. NM is orally administered at a high dose of 290 mg due to its low solubility and poor dissolution rate at pH > 3, as well as gut-wall metabolism limiting its bioavailability. Self-emulsifying drug delivery systems (SEDDSs) of NM were developed in the current study to improve its oral bioavailability. The oily vehicle (clove oil) was selected based on the solubility of NM, while the surfactant and the cosurfactant were selected based on the turbidimetric analysis. Three different sets were screened for surfactant selection in the preparation of SEDDS formulations, the first set containing Cremophor® EL alone as the surfactant, the second set containing a mixture of Cremophor® EL (surfactant) and Caproyl® PGMC (cosurfactant), and the third set containing a mixture of Cremophor® EL (surfactant) and Capmul® MCM C8 (cosurfactant). Propylene glycol was used as the cosolubilizer in the preparation of SEDDSs. A series of studies, including the construction of ternary phase diagrams to determine the zone of emulsification, thermodynamic stability studies (involving dilution studies, freeze-thaw, and heating-cooling studies), turbidimetric analysis, and physicochemical characterization studies were conducted to identify the two most stable combinations of SEDDSs. The two optimized SEDDS formulations, TP16 and TP25, consisted of clove oil (45% w/w) and propylene glycol (5% w/w) in common but differed with respect to the surfactant or surfactant mixture in the formulations. TP16 was prepared using a mixture of Cremophor® EL (surfactant) and Caproyl® PGMC (cosurfactant) in a 4:1 ratio (50% w/w), while TP25 contained only Cremophor® EL (50% w/w). The mean globule sizes were 239.8 ± 77.8 nm and 204.8 ± 2.4 nm for TP16 and TP25, respectively, with an emulsification time of <12 s for both formulations. In vitro drug dissolution studies performed at different pH conditions (3.0, 4.5, 6.8) have confirmed the increase in solubility and dissolution rate of the drug by TP16 and TP25 at all pH conditions compared to plain NM. An oral pharmacokinetic study in female Wistar rats showed that the relative bioavailability (Frel) values of TP16 and TP25 over the plain NM were 2.18 (p < 0.05) and 2.24 (p < 0.01), respectively.

Enhanced Sperm Quality in Aged Broiler Breeder Roosters with Organic Selenium and Selenium Nanoparticles: A Comparative Bioavailability Study.

This study aimed to investigate the impact of dietary selenium treatments on various sperm parameters and antioxidant responses in aged roosters to determine the relative bioavailability value (RBV) and optimize selenium supplementation. Over 40days, starting from week 47 of age, the roosters were fed ten experimental diets, including a basal diet without selenium supplement and nine selenium-treated diets. These selenium-treated diets comprised three different selenium sources (selenium selenite: SS; SelPlex: Se-enriched yeast; selenium nanoparticles: SeNPs), each with three levels of selenium supplements (0.15, 0.30, and 0.45mg/kg). Statistical analysis indicated significant treatment effects on all measured parameters except sperm volume. Sperm motility and viability increased linearly with higher dietary selenium levels. The relative bioavailability values (RBV) of SelPlex and SeNPs compared to SS were estimated using the slope ratio and exponential regression methods. Using the slope-ratio method, the RBV for sperm volume was 457% for SelPlex and 314% for SeNPs, compared to SS. Using exponential regression, the RBV of SelPlex and SeNPs for various parameters were as follows: for MDA (malondialdehyde), 260% and 317%; for TAC (total antioxidant capacity), 447% and 294%; for sperm morphology, 227% and 423%; and for sperm concentration, 346% and 298%, respectively. Principal component analysis revealed strong correlations between sperm motility, viability, and antioxidant parameters, with weaker associations observed between sperm volume and testosterone. Optimization using a desirability function identified 0.45mg/kg selenium supplementation using SeNPs as optimal, maximizing sperm parameters and antioxidant responses while minimizing MDA and morphology. These findings offer valuable insights into effective selenium supplementation strategies to enhance avian reproductive health in aged roosters.

A comparative study between curcumin and curcumin nanoparticles on reproductive performance and antioxidant system of aged roosters

Increased lipid peroxidation and decreased antioxidant status can result in reduced reproductive activity and fertility in aged male broiler breeders. This study was conducted to evaluate the effects of curcumin supplements (natural or nanoparticles) on the sperm characteristics, antioxidant system, fertility, and hatchability of aged roosters (54-64 wk), and to estimate the relative bioavailability value (RBV) of nano-curcumin on the measured parameters including the hypo-osmotic swelling test (HOST), motility, viability, sperm count, volume, the concentration of testosterone, glutathione peroxidase (GPx), and superoxide dismutase (SOD), diameter of the spermatogenic tube (DST), epithelium thickness (EpiTh), spermatogonia count (SPcount), fertility, hatchability, and relative weight of testis (RW-testis). A total of 30 roosters were individually caged and randomly assigned to 5 treatments comprising control (without curcumin as the basal diet), basal diet + 15 mg/kg curcumin (CUR15), basal diet + 30 mg/kg curcumin (CUR30), basal diet + 15 mg/kg nano-curcumin (Nano15), and basal diet + 30 mg/kg nano-curcumin (Nano30) for 10 wk. The slope ratio method was used to estimate the bioavailability of nano-curcumin by regressing each response on supplemental curcumin intake. Increasing dietary curcumin (P < 0.001) elicited a linear response to all studied traits. The RBV for volume, viability, motility, HOST, RW-testis, and GPx were estimated as 135 (CI: 115-156%), 143 (CI: 114-173%), 159 (CI: 122-196%), 132 (CI: 107-157%), 195 (CI: 126-264%), 176 (CI: 103-249%), and 178% (28-328%), respectively. Our findings revealed that curcumin nanoparticles enhance the reproductive efficiency of aged breeder roosters. In addition, the curcumin nanoparticles RBV exceeded that of natural curcumin, suggesting that lower concentrations of curcumin nanoparticles could have a significant effect on reproductive characteristics.

Research Note: Relative bioavailability of zinc in zinc hydroxychloride for chicks

A chick assay was conducted to determine the effects of Zn source on performance and to establish a Zn relative bioavailability value (RBV) for a new source of Zn hydroxychloride. In the assay, 8-day-old chicks were fed a Zn-deficient soy protein concentrate diet supplemented with 0, 7, and 15 mg Zn/kg from feed grade ZnSO4 monohydrate for 14 d to establish a standard response curve. The same basal diet was supplemented with 3, 7, and 10 mg Zn/kg from a new Zn hydroxychloride (SAMZn). A second source of Zn hydroxychloride (IBZn) was supplemented at 10 mg Zn/kg as a direct comparison to the highest level of SAMZn. Weight gain increased (P < 0.05) with increasing Zn level, regardless of source. Weight gain of chicks fed 7 mg Zn/kg from SAMZn was not different (P > 0.05) from chicks fed 15 mg Zn/kg from ZnSO4. Weight gain was not different (P > 0.05) when comparing the 2 sources of Zn hydroxychloride supplemented at 10 mg Zn/kg. Tibia ash Zn and total tibia Zn were increased (P < 0.05) by all Zn sources and responded linearly (P < 0.05) to Zn supplementation from ZnSO4 and SAMZn. Total tibia Zn concentration was not different (P > 0.05) for chicks fed 10 mg Zn/kg from either source of Zn hydroxychloride. Multiple linear regression of total tibia Zn on supplemental Zn intake (R2 = 0.95) resulted in a RBV of 115% for SAMZn compared with ZnSO4 (set at 100%). The RBV of SAMZn was higher (P < 0.05) than ZnSO4. In conclusion, relative bioavailability of Zn (based on tibia Zn) in Zn hydroxychloride from SAMZn was higher than feed grade ZnSO4 based on multiple regression slope-ratio analysis and was similar to that of IBZn Zn hydroxychloride based on tibia Zn responses to 10 mg/kg supplemental dietary Zn.

Innovative accumulative risk assessment of co-exposure to Cd, As, and Pb in contaminated rice based on their in vivo bioavailability and in vitro bioaccessibility

The consumption of cadmium (Cd), arsenic (As), and lead (Pb) co-contaminated rice exposes humans to multiple heavy metals simultaneously, with relative bioavailability (RBA) and bioaccessibility (BAc) being important determinants of potential health risks. This study evaluated the relationship between in vivo RBA and in vitro BAc of Cd, As, and Pb in rice and their cumulative risk to humans. A total of 110 rice samples were collected in Zhejiang Province, China, and 10 subsamples with varying concentration gradients were randomly selected to measure RBA using a mouse model (liver, kidney, femur, blood, and urine as endpoints) and BAc using four in vitro assays (PBET, UBM, SBRC, and IVG). Our results indicated that Cd-RBA varied from 21.2 % to 67.5 %, As-RBA varied from 23.2 % to 69.3 %, and Pb-RBA varied from 22.2 % to 68.9 % based on mouse liver plus kidneys. The BAc values for Cd, As, and Pb in rice varied according to the assay. Compared to Cd and As, Pb exhibited a lower BAc in the gastric (GP) and intestinal (IP) phases. According to the relationship between the BAc and RBA values, IVG-GP (R2 = 0.92), SBRC-IP (R2 = 0.73), and UBM-GP (R2 = 0.80) could be used as predictors of Cd-, As-, and Pb-RBA in rice, respectively. The health risks associated with co-exposure to Cd, As, and Pb in contaminated rice for both adults and children exceeded the acceptable threshold, with Cd and As being the primary risk factors. The noncarcinogenic and carcinogenic risks were markedly reduced when the RBA and BAc values were incorporated into the risk assessment. Due to the risk overestimation inherent in estimating the risk level based on total metal concentration, our study provides a realistic assessment of the cumulative health risks associated with co-exposure to Cd, As, and Pb in contaminated rice using in vivo RBA and in vitro BAc bioassays.

Cadmium and lead bioavailability to poultry fed with contaminated soil-spiked feed

Geophagy is common for free-range chickens, however, the relative bioavailability (RBA) of heavy metals in contaminated soils consumed by chickens has not fully investigated. In this work, chickens were fed diets increasingly spiked with a contaminated soil (Cd = 105, Pb = 4840 mg kg−1; 3, 5, 10, 20 and 30 % of overall feed by weight), or Cd/Pb reagent spikes (from CdCl2 or Pb(Ac)2), for 23 d. After the study period, chicken liver, kidney, femur and gizzard samples were analyzed for Cd and Pb concentrations, and organ/tissue metal concentrations were used to calculate Cd and Pb RBA. Linear dose response curves (DRCs) were established for both Cd/Pb reagents-spiked and soil-spiked treatments. Femur Cd concentrations of soil-spiked treatments were two times of Cd-spiked treatments with similar feed Cd levels, while feed spiked with Cd or Pb also resulted in elevated Pb or Cd concentrations in some organ/tissues. Metal RBA was calculated using three different methods. Most Cd and Pb RBA values were in the range 50–70 %, with the chicken gizzard as a potential endpoint for bioaccessible Cd and Pb. Cadmium and Pb bioavailability values can help with more precise estimation of Cd and Pb accumulation in chicken following heavy metal-contaminated soil ingestion, with overall results helping to protect human health.

Comparison of zinc bioavailability in zinc-glycine and zinc-methionine chelates for broilers fed with a corn-soybean meal diet.

The objective of this study was to compare the bioavailability of zinc (Zn) from zinc-glycine (Zn-Gly) and zinc-methionine (Zn-Met) as compared with zinc sulfate (ZnSO4) used as a standard in broilers. A total of 1,200 one-day-old male broilers (Cobb 500) were randomly allotted to one of 10 treatments with eight replicate cages of 15 birds each. The broilers were fed a corn-soybean meal basal diet (containing 26.46mg Zn/kg; control) or the basal diet added with 40, 80, and 120mg Zn/kg as Zn-Gly, Zn-Met, or ZnSO4 for 14days. The relative bioavailability value (RBV) was calculated based on multiple linear regression slope ratios of Zn concentrations in tibia and pancreas, pancreas metallothionein (MT) concentration, and pancreas MT mRNA abundance on added Zn intake. When comparing the control with all Zn-supplemented treatments, Zn addition did not significantly affect average feed intake and bodyweight gain during days 1-14 (p > 0.10). However, Zn concentrations in the tibia, pancreas, and liver and pancreas MT concentration and MT mRNA abundance increased in all Zn-supplemented treatments compared with the control (p < 0.05), and these indices increased linearly (p < 0.001) with increasing added Zn levels on days 7 and 14. The RBV of Zn as Zn-Met was similar to that as Zn-Gly or ZnSO4 (p > 0.40) on days 7 and 14, based on tibia and pancreas Zn. In contrast, on days 7 and 14, the RBVs of Zn were in the following order: Zn-Met > Zn-Gly > ZnSO4 (p < 0.05), based on pancreas MT concentration. The bioavailable Zn from Zn-Met was 1.20 or 1.25 times that from Zn-Gly on day 7 or 14, respectively, evaluated by pancreas MT content. The RBV of Zn as Zn-Met was similar to that as Zn-Gly or ZnSO4 on day 7, whereas it was higher than that as Zn-Gly or ZnSO4 on day 14, based on pancreas MT mRNA abundance. In conclusion, Zn-Met had higher bioavailable Zn than Zn-Gly for the starter broilers fed with the corn-soybean meal diet, using pancreas MT concentration as the response criterion.

Relative Bioavailability Value (RBV) of mineral supplementation in the broilers’ diet contains wheat and barley as sources of non-starch polysaccharide

ABSTRACT The experiment was conducted for investigating the effect of Non-Starch Polysaccharide (NSP) feed containing wheat and barley on relative bioavailability values (RBVs) of minerals and supplementation in the broilers’ diet. A total of 72 male broiler chickens (Ross 308) were arranged with 4 repetitions (6 birds per each replicated in the metabolic cages) on the 3 treatment diets. The experimental diets contain one control diet and 2 diets with formulation of 25% wheat and 20% barley. Estimated relative mineral bioavailability values (RMBVs) were based on daily dietary mineral intake. The RBVs of Ca, P, Cu, Mn, Fe, and Zn were 44, 120, 17, 0.37, 125, and 15.38, respectively for dietary-containing wheat. Data showed that NSP contain a diet effect on bone characteristics and seed or index tibiae bone (P < 0.05). RMBVs of Ca, P, Mn, Fe, and Zn for a diet including wheat were 65.20, 84.96, 21.05, 8.50, and 2.56, respectively based on the tibia bone. Also, RMBVs of tibia bone minerals, such as Ca, P, Mn, Fe, and Zn from a diet containing barley, were 53.60, 43.33, 40.60, 44.16, and 44.69, respectively. The results of experiments indicated that Ca, P, and Fe have highly RMBVs concerning the amount of NSP contained in barley.

Relative Bioavailability of Trace Minerals in Production Animal Nutrition: A Review.

Simple SummaryThis is a comprehensive review containing the most up-to-date information on the relative bioavailability of selected trace minerals (copper, iron, manganese and zinc) used in ruminant, poultry and swine nutrition. Inorganic and organic forms of the trace minerals are included, and the differences between the product types are highlighted. Building on previously published tables and data, this review incorporates studies on newly developed products and concepts not previously discussed. Extensive data tables are included, providing a valuable reference guide. Methods to calculated relative bioavailability of the minerals are discussed and reasons for potential variance are noted. Detailed background information on uptake mechanisms to aid understanding of mineral transport is also contained in the current review.The importance of dietary supplementation of animal feeds with trace minerals is irrefutable, with various forms of both organic and inorganic products commercially available. With advances in research techniques, and data obtained from both in-vitro and in-vivo studies in recent years, differences between inorganic and organic trace minerals have become more apparent. Furthermore, differences between specific organic mineral types can now be identified. Adhering to PRISMA guidelines for systematic reviews, we carried out an extensive literature search on previously published studies detailing performance responses to trace minerals, in addition to their corresponding relative bioavailability values. This review covers four of the main trace minerals included in feed: copper, iron, manganese and zinc, and encompasses the different types of organic and inorganic products commercially available. Their impact from environmental, economic, and nutritional perspectives are discussed, along with the biological availability of various mineral forms in production animals. Species-specific sections cover ruminants, poultry, and swine. Extensive relative bioavailability tables cover values for all trace mineral products commercially available, including those not previously reviewed in earlier studies, thereby providing a comprehensive industry reference guide. Additionally, we examine reasons for variance in reported relative bioavailability values, with an emphasis on accounting for data misinterpretation.

Intranasal delivery of lipid-based nanosystems as a promising approach for brain targeting of the new-generation antiepileptic drug perampanel

Perampanel (PER), a new-generation antiepileptic drug effective against different types of seizures, has already demonstrated a potential in status epilepticus therapy. Considering the growing interest of intranasal (IN) administration for nose-to-brain delivery, PER could be envisioned as a good candidate for this route, especially if formulated in a lipid-based nanosystem. With that purpose, a hydrophobic formulation (FO1.2) and a self-microemulsifying drug delivery system (SMEDDS) (FH5) loaded with PER were developed and characterized. Following PER IN administration (1 mg/kg) to mice, its pharmacokinetics was characterized and compared with intravenous and oral routes. Histopathological toxicity was also examined after a 7-day repeated dose study. FH5 homogeneously formed nanodroplets upon dispersion (20.07 ± 0.03 nm), showing a sustained in vitro PER release profile up to 4 h. By IN route, PER brain delivery was more extensive with FH5 (Cmax and AUC of 52.32 ng/g and 190.35 ng.h/g for FO1.2; 93.87 ng/g and 257.75 ng.h/g for FH5). Maximum brain concentration and total brain exposure were higher than those obtained after oral dosage, with maximum PER concentrations reached significantly faster than post-oral administration (15 min vs 2 h). An improvement in PER plasmatic concentration was also obtained, demonstrated by high relative bioavailability values (134.1% for FH5 and 107.8% for FO1.2). PER absolute plasma bioavailability after IN delivery was 55.5% for FH5 and 44.6% for FO1.2, ensuring a somewhat improved targeting of PER to the brain by the IN route compared to the IV route. No signs of toxicity were found by histopathologic evaluation. Results suggest that IN administration of PER might be a feasible and safe approach for acute and chronic epilepsy management, especially using delivery systems as SMEDDS.

Iron Bioavailability from Ferrous Ammonium Phosphate, Ferrous Sulfate, and Ferric Pyrophosphate in an Instant Milk Drink-A Stable Isotope Study in Children.

Ferrous ammonium phosphate (FAP) is an iron salt that has been developed for the fortification of food matrices sensitive to color and flavor changes. The objective of the study was to measure iron absorption from FAP in young children and compare it to a previous evaluation of FAP in young women. A double-blind randomized crossover study with two parallel arms was used to evaluate the iron absorption from FAP added to reconstituted milk powder in comparison to that from ferrous sulfate (FeSO4) and ferric pyrophosphate (FePP). Iron absorption was measured in 39 children aged 3- to 6-years-old using erythrocyte incorporation of stable Fe isotopes (57Fe, 58Fe). The geometric mean iron absorption in iron replete children from FAP, FeSO4 and FePP from milk was 8.3%, 7.6% and 2.1%, respectively. Iron absorption from FAP and FeSO4 fortified milk was not significantly different (p = 0.199); however, it was significantly higher than from FePP fortified milk (p < 0.001). Iron bioavailability from FAP and FePP relative to FeSO4 (relative bioavailability (RBV)) was 110% and 33%, respectively. The RBV of FAP (110%) in iron replete children was higher than previously reported RBV (71%) in mainly iron deficient women. The difference in iron status between the children and women in the respective studies may explain the different RBV values and is discussed.

Systematic Review on the Effectiveness of Strategies for Increasing Insulin Bioavailability in Oral Route Delivery Systems Based on Manufacturing Techniques and Materials Used

Diabetes is a metabolic disease characterized by hyperglycemia due to impaired insulin secretion, insulin action, or both. All patients with type 1 diabetes and many type 2 diabetes require insulin therapy to achieve reasonable glycemic control. During this time, insulin is given through the subcutaneous injection route because it can be destroyed by gastric acid when given orally. Until now, many studies have developed oral insulin therapy using various delivery system strategies. This systematic literature review aims to answer several questions about the effect of technique and material on increasing oral insulin bioavailability and the best technique and type of material that can produce the best oral insulin bioavailability. We searched for published articles regarding the development of oral route insulin. Bioavailability parameters were assessed based on plasma insulin levels for relative bioavailability values and/or plasma glucose levels for pharmacological bioavailability values. Conclusion: The manufacturing technique in the delivery system affects insulin stability in maintaining its conformation to provide a therapeutic effect. The type of substance affects insulin bioavailability through its properties in paving the way for insulin across various barriers in the digestive tract. To date, the best results in the development of oral insulin have obtained oral insulin bioavailability of 73.10% achieved by mesoporous silica nanoparticles (MSN) delivery system with layer-by-layer technique coated with [poly (methacrylic acid-co-vinyl triethoxylsilane)] (PMV)].&#x0D; Keywords: bioavailability, diabetes, insulin, nanoparticles, oral delivery system.

Albendazole Nanocrystal-Based Dissolving Microneedles with Improved Pharmacokinetic Performance for Enhanced Treatment of Cystic Echinococcosis.

Cystic echinococcosis (CE) is a zoonosis caused by Echinococcus spp., affecting both humans and animals' lives. Current treatment of CE by oral administration of albendazole (ABZ) is hampered by several limitations. The poor aqueous solubility and the rapid metabolism of ABZ in the liver are the main issues, leading to lack of efficacy of the treatment. In the present study, we developed a nanocrystalline (NC) formulation of ABZ to be delivered intradermally using dissolving microneedles (DMNs). The NC formulation was developed using milling in an ultrasmall-scale device. Following several screenings, Pluronic F127 was selected as a suitable stabilizer, producing NCs with around 400 nm in size with narrow particle distribution. The crystallinity of ABZ was maintained as observed by DSC and XRD analysis. The NC approach was able to improve the dissolution percentage of ABZ by approximately three-fold. Furthermore, the incorporation of NCs into DMNs using the combination of poly(vinylpyrrolidone) and poly(vinyl alcohol) formed sharp needles with sufficient mechanical strength and insertion properties. Dermatokinetic studies revealed that >25% of ABZ was localized in the dermis of excised neonatal porcine skin up to 48 h after DMN administration. In in vivo pharmacokinetic studies, the AUC and relative bioavailability values of ABZ delivered by NC-loaded DMNs were found to be significantly higher than those obtained after oral administration of coarse suspension of ABZ or ABZ-NCs, as well as DMNs delivering coarse ABZ as indicated by the relative bioavailability values of >100%. Therefore, the combination approach developed in this study could maintain the systemic circulation of ABZ, which could be possibly caused by avoiding the first-pass metabolism in the liver. This could be beneficial to improve the efficacy of ABZ in CE treatment.

Bioavailability of the dl-methionine and the calcium salt of dl-methionine hydroxy analog compared with l-methionine for nitrogen retention in starter pigs.

Two nitrogen balance studies were conducted to evaluate the relative bioavailability values (RBV) of dl-methionine (dl-Met) and dl-methionine hydroxy analog calcium salt (MHA-Ca) to l-methionine (l-Met) as Met sources fed to pigs. In experiment 1, 42 pigs were assigned to 7 treatments feeding with basal diet (BD) formulated to be deficient in Met (0.22% standardized ileal digestible basis) but adequate in other amino acids. Diets included (1) BD, (2) BD + 0.025% dl-Met, (3) BD + 0.050% dl-Met, (4) BD + 0.075% dl-Met, (5) BD + 0.025% l-Met, (6) BD + 0.050% l-Met, and (7) BD + 0.075% l-Met. Increasing levels of l-Met and dl-Met enhanced N retained (g/d) and N retention (% of intake) linearly (P < 0.01). Using a linear slope ratio procedure, a product-to-product RBV of dl-Met compared with l-Met was 94% (95% confidence limits: 65% to 123%) based on N retained expressed as g/d and 99% (95% confidence limits: 70% to 128%) for N retention expressed as % of intake. In experiment 2, 42 pigs were allotted to 7 treatments in another N-balance trial. Diets included (1) BD, (2) BD + 0.025% l-Met, (3) BD + 0.050% l-Met, (4) BD + 0.075% l-Met, (5) BD + 0.030% MHA-Ca, (6) BD + 0.060% MHA-Ca, and (7) BD + 0.089% MHA-Ca. An increase in dietary inclusion rates of l-Met increased (P < 0.01) N retained (g/d) linearly while increasing levels of MHA-Ca had no effects (P > 0.05) on N retained (g/d) and N retention (% of intake). Using linear slope-ratio regression, the RBV of MHA-Ca compared with l-Met was 70% (95% confidence limits: 59% to 81%) on a product-to-product basis or 83% on equimolar basis based on N retained expressed as g/d. Overall, the mean RBV of dl-Met to l-Met of 97% (95% confidence limits cover 100%) indicated that dl-Met and l-Met are equally bioavailable as Met sources in pigs. Compared with l-Met, the RBV of MHA-Ca was lower at 70% (95% confidence limits: 59% to 81%) on a product-to-product basis or 83% on equimolar basis in starter pigs.

Phosphorus digestibility and relative phosphorus bioavailability in two dried black soldier fly larvae meals and a defatted black soldier fly larvae meal in broiler chickens

Two chicken assays were conducted to determine P availability, using three different approaches, for 2 black soldier fly larvae meals (BSFL 1 and 3) and one partially-defatted BSFL. Experiment 1 was conducted to determine ileal P digestibility and total tract P retention. Three experimental diets containing a BSFL as the only source of P were fed to broiler chickens from 19 to 22 days of age. Each diet contained 0.25% total dietary P. Ileal digesta and excreta were collected on day 22. Ileal digestibility of P was 87%, 75%, and 88% for BSFL 1, BSFL 3, and partially-defatted BSFL, respectively. Total tract P retention was 87%, 73%, and 85% for BSFL 1, BSFL 3, and partially-defatted BSFL, respectively. The objective of experiment 2 was to determine the relative bioavailability of P in the 3 insect meals relative to KH2PO4 using a chicken bone ash bioassay. Chickens were fed one of nine dietary treatments from 8 to 22 days of age. These diets included a P-deficient cornstarch-dextrose-SBM based diet (0.14% nonphytate P) or that diet supplemented with 0.05% or 0.10% P from KH2PO4, 7% or 14% BSFL 1, 8%, or 16% BSFL 3, and 8% or 16% partially-defatted BSFL. The slope-ratio method using multiple regression for tibia ash regressed on supplemental P intake was used to calculate the relative bioavailability of P where values for BSFL 1, BSFL 3, and partially-defatted BSFL were 54%, 51%, and 57%, respectively, relative to KH2PO4. The results of this study indicated that availability of P in BSFL based on ileal P digestibility and total tract P retention values was high, whereas relative bioavailability values for P based on tibia ash were approximately 20 to 30 percentage units lower.

Development and pharmacokinetic evaluation of chewable doxycycline tablets in Beagle dogs: comparison with a commercial formulation and evaluation of co-administration with vitamin supplement on the bioavailability

Doxycycline (DOX) is the antibiotic of choice for the treatment of canine monocytic ehrlichiosis (CME), one of the main infectious diseases affecting dogs. Despite the therapeutic simplicity, the need for long-term use of DOX tablets (28 days) and gastrointestinal effects may pose problems. The aim of the study was to develop a DOX chewable tablet, evaluate its palatability and pharmacokinetic profile in comparison with a commercial formulation, Doxifin®, and evaluate the influence of co-administration with vitamin supplement on the bioavailability of doxycycline. The AUC0-t values found for DOX chewable tablets (13.85 ± 3.81 μg.h/mL) and Doxifin® (15.88 ± 4.38 μg.h/mL) did not differ significantly (p<0.05). The co-administration of the vitamin supplement Hemolitan® influenced the pharmacokinetic profile of DOX, leading to a decrease in bioavailability for chewable DOX tablets and Doxifin®, with relative bioavailability values (F) of 64% and 62%, respectively. Palatability evaluations confirmed the palatability of the chewable tablets. Therefore, a DOX chewable tablet is an important alternative that can overcome some of the challenges associated with the characteristic bitter taste of doxycycline, with considerable reduction animal stress, and with plasma doxycycline concentrations equivalent in practical terms to a conventional product.

Utilization of Methionine Sources for Growth and Met+Cys Deposition in Broilers.

Simple SummaryMethionine (Met) is the first limiting amino acid in broiler feeds and for balancing dietary Met and methionine+cysteine (Met+Cys) levels. DL-2-hydroxy-4-methylthio butanoic acid (HMTBA) and DL-methionine (DLM) are typical feed additives. The relative bioavailability value (RBV) describes the nutritional value of HMTBA relative to DLM and is important for adequate, precise, and cost-effective broiler nutrition. The current broiler feeding trial revealed an average RBV of 63% compared to DLM and the inclusion of an internal standard into the experimental design allowed for validation of the methodological approach. Evaluation of the utilization of supplemental Met sources for Met+Cys deposition in body protein provided further evidence for a higher efficiency and, thus, nutritional value of DLM over HMTBA.Knowledge about the nutritional value of methionine sources is highly important for their appropriate application in terms of animal and economic performance. Therefore, a broiler feeding trial was conducted to determine the relative bioavailability value (RBV) of DL-2-hydroxy-4-methylthio butanoic acid (HMTBA) compared to DL-methionine (DLM). DLM diluted to 65% purity (DLM65) served as the internal standard, with a known RBV of 65%. A total of 1920 d-old male broilers were used in the three-phase feeding trial comprising 16 treatments including a basal, Met+Cys-deficient diet and 5 graded DLM, HMTBA, or DLM65 levels. Growth performance and carcass quality data were subjected to multi-exponential regression analysis. Increasing levels of any Met source significantly improved all performance parameters compared to the negative control (p < 0.05). Across all performance parameters, the RBV of HMTBA was 63% and that of DLM65 was 58%. All RBV estimates of HMTBA and DLM65 were significantly lower than 88% (p < 0.05). Cumulative efficiency of DLM for Met+Cys deposition in body protein was higher than that of HMBTA at any dose, confirming the determined RBV. Using DLM65 as an internal marker allowed for validation of the methodology.

Effects of Borneol on the Release of Compound Danshen Colon-Specific Osmotic Pump Capsule In Vitro and Pharmacokinetics Study in Beagle Dogs.

Borneol can enhance the bioavailability of several other drugs by opening the blood-brain barrier and inhibiting P-glycoprotein (P-gp) efflux. However, whether borneol will impact the bioavailability and the mechanism of compound Danshen colon-specific osmotic pump capsule (CDCOPC) remains unclear. This study aimed to determine the effects of borneol on the in vitro release and in vivo pharmacokinetic characteristics of CDCOPC. Besides, the in vitro release behavior of CDCOPC was further assessed by chromatographic fingerprints. The in vitro release studies showed that borneol followed the zero-order release and hardly impacted the in vitro release of Salvia miltiorrhiza and Panax notoginseng in CDCOPC. Moreover, as revealed from the similarity results of fingerprints, the in vitro release of different components of CDCOPC was almost simultaneous. Compared with the commercially available tablets, the pharmacokinetics studies suggested that both CDCOPCs containing and lacking borneol could significantly prolong the retention time of these effective components; their average relative bioavailability values increased to 448.70% and 350.97%, respectively. Notably, borneol significantly improved the relative bioavailability of some components of CDCOPC, such as salvianolic acid B (SAB), tanshinone IIA (Tan IIA), notoginsenoside R1 (R1), ginsenoside Rg1 (Rg1), and ginsenoside Re (Re) from CDCOPC, while it slightly impacted ginsenoside Rb1 (Rb1) and ginsenoside Rd (Rd). Summarily, borneol is capable of improving the bioavailability of some effective components in CDCOPC, which is critical to design with CDCOPC for enhanced bioavailability. This study could also help reveal the composition principle of the compound Danshen formula (CDF).

Bioavailability of the calcium salt of dl-methionine hydroxy analog compared with dl-methionine for nitrogen retention and the preference of nursery pigs for diets based on the 2 forms of methionine.

Experiments were conducted to determine the relative bioavailability (RBV) of the calcium salt of the hydroxy analog of dl-methionine (MHA-Ca, 84%) to dl-methionine (dl-Met, 99%) as Met sources fed to pigs. In experiment 1, 42 crossbred barrows (initial BW of 15.0 ± 0.7 kg) were allotted to 7 treatments in an N-balance study. The basal diet (BD) was formulated to contain 15.4% CP and 0.22% Met (70% of requirement). Diets included (1) BD, (2) BD + 0.025% dl-Met, (3) BD + 0.050% dl-Met, (4) BD + 0.075% dl-Met, (5) BD + 0.038% MHA-Ca, (6) BD + 0.077% MHA-Ca, and (7) BD + 0.115% MHA-Ca. An increase in dietary inclusion rates of both Met sources linearly increased (P < 0.01) N retained (g/d) and N retention (% of intake). Using linear slope-ratio regression, the RBV value of MHA-Ca to dl-Met for N retained (g/d) was 63.0% on a product-to-product basis (75.0% on an equimolar basis). In experiment 2, 40 crossbred barrows (initial BW of 15.5 ± 1.5 kg) were allotted to 5 treatments in another N-balance study. The BD was formulated to contain 17.0% CP and 0.22% Met (70% of requirement). Diets included (1) BD, (2) BD + 0.030% dl-Met, (3) BD + 0.060% dl-Met, (4) BD + 0.046% MHA-Ca, and (5) BD + 0.092% MHA-Ca. Increasing levels of dl-Met or MHA-Ca increased N retained (g/d) and N retention (% of intake) linearly (P < 0.001) and quadratically (P < 0.05). Using linear slope-ratio regression, a product-to-product RBV value of MHA-Ca to dl-Met was 68.4% (81.4% on an equimolar basis) for N retained (g/d). In experiment 3, 276 pigs (12 barrow and 11 gilt replicates; initial BW of 7.09 ± 1.1 kg) were used in 3 diet preference studies. Pigs were randomly allotted to 1 of 3 treatment comparisons of feed choice: (1) BD (0.23% Met) or BD + 0.07% dl-Met; (2) BD or BD + 0.0825% MHA-Ca, and (3) BD + 0.07% dl-Met or BD + 0.0825% MHA-Ca. Pigs consumed a higher percentage (55 vs. 45%; P = 0.008) of their total feed intake from the diet supplemented with 0.07% dl-Met in Comparison 1, but a lower percentage (45 vs. 55%; P = 0.003) of their total feed intake from the diet supplemented with 0.0825% MHA-Ca in Comparison 2. There was no diet preference for dl-Met or MHA-Ca in Comparison 3. The observed Met source preference differences occurred in the barrow replicates but not in the gilt replicates. These results demonstrated the mean RBV of MHA-Ca to dl-Met of 65.7% on a product-to-product (wt/wt) basis or 78.2% on an equimolar basis and that a preference for Met sources was observed in barrows but not in gilts.