Additional file 1 of In-vitro susceptibility and ex-vivo evaluation of macrocyclic lactone endectocides sub-lethal concentrations against Plasmodium vivax oocyst development in Anopheles arabiensis

Additional file 1: Table S1. Preparation of ivermectin, doramectin, and moxidectin concentrations (1-1000ng/mL) in spiked cattle blood. Table S2. Preparation of ivermectin, doramectin, and moxidectin sublethal concentrations (LC25 and LC5) in spiked Plasmodium vivax infected blood. Annex I. Malaria Patient’s Information Sheet. Annex II. Study participant informed Consent

<i>In vitro</i> model to assess the adsorption of oral veterinary drugs to mycotoxin binders in a feed- and aflatoxin B1-containing buffered matrix

<p>Mycotoxin binders are feed additives which are mixed in the feed to adsorb mycotoxins and thereby reducing their toxic effects on animals. Interactions with orally administered veterinary medicinal products, such as antimicrobials or coccidiostats, have been reported previously. This paper describes an <i>in vitro</i> model to screen the interaction between mycotoxin binders and veterinary drugs with respect to the non-specific binding of drugs. It is designed as a static setup using a single concentration of drug and binder in a feed-containing or a feed-plus-mycotoxin-containing matrix, buffered at different pH values. The model was applied to two frequently used antimicrobials in veterinary medicine, doxycycline (DOX) and tylosin (TYL), one major mycotoxin, aflatoxin B1 (AFB1), and four mycotoxin binders. Proportions of feed, DOX or TYL, AFB1, and binder are equivalent to the <i>in vivo</i> situation for broiler chickens, while pH and volume of the buffer are representative of the gastrointestinal tract of chickens. A substantial binding of DOX (~ 88%) and TYL (~ 66%) to the feed-matrix was observed. For the mycotoxin binders, similar results were obtained for DOX and TYL; more specifically up to an inclusion rate of 20 g binder/kg feed, no significant binding was demonstrated, determined as the free concentration of DOX and TYL. A single exception was noticed for TYL and one specific bentonite-based mycotoxin binder, for which no significant interaction could be demonstrated up to 10 g binder/kg but there was an effect at 20 g/kg. In all cases, there was no competition between the tested drugs DOX or TYL and the mycotoxin AFB1 for binding to the bentonite-based mycotoxin binder.</p

Comparative Oral Bioavailability, Toxicokinetics, and Biotransformation of Enniatin B1 and Enniatin B in Broiler Chickens

A toxicokinetic study of the Fusarium mycotoxins enniatin B1 (ENN B1) and enniatin B (ENN B) was performed in broiler chickens. Each animal received ENN B1 or B orally via an intracrop bolus and intravenously at a dose of 0.2 mg/kg body weight. Both enniatins were poorly absorbed after oral administration, with absolute oral bioavailabilities of 0.05 and 0.11 for ENNs B1 and B, respectively. Both enniatins were readily distributed to the tissues, with mean volumes of distribution of 25.09 and 33.91 L/kg for ENNs B1 and B, respectively. The mean total body clearance was rather high, namely, 6.63 and 7.10 L/h/kg for ENNs B1 and B, respectively. Finally, an UHPLC-HRMS targeted approach was used to investigate the phase I and II biotransformations of both mycotoxins. Oxygenation was the major phase I biotransformation pathway for both ENNs B1 and B. Neither glucuronide nor sulfate phase II metabolites were detected

Chestnut Wood Tannins in Broiler Diets: Pharmacokinetics, Serum Levels during Rearing, and Intestinal Absorption Pattern of Gallic Acid

Studies on the bioavailability, serum levels, and absorption of hydrolyzable tannin compounds are lacking. In this study, we performed a pharmacokinetic trial, measured the serum levels of compounds in broilers that were reared with different feed added or not with tannins, and tested the digestibility of tannins throughout the intestinal tract. Only gallic acid and 4-O-methyl gallic acid were found in the serum. Moreover, gallic acid showed a 41.8% absolute oral bioavailability and a 72.3% relative bioavailability of gallic acid from chestnut extract compared to the standard. The rapid metabolization caused alternating serum levels during the day and night. These patterns were not affected by the feed type or the previous addition of tannins in the feed. The absorption and metabolization in the intestines occurred gradually throughout the intestinal tract. The latter was true for gallic acid as well as ellagic acid, which was not found in the serum. We can conclude that components from chestnut tannins are absorbed throughout all components of the intestinal tract and are eliminated quickly with little interaction from the feed and previous addition of tannins. Moreover, ellagic acid seems to be absorbed but would remain accumulated in the intestinal tissue or be metabolized by the microbiome

Additional file 1: of Pharmacokinetic and urinary profiling reveals the prednisolone/cortisol ratio as a valid biomarker for prednisolone administration

Biotransformation pathway of prednisolone into prednisone, 20α-dihydroprednisolone and 20β-dihydroprednisolone by hydroxysteroid dehydrogenases. Schematic representation of the enzymatic mechanisms, underlying the formation of the major prednisolone-related metabolites. Involved enzymes concern various hydroxysteroid dehydrogenases (HSD). (TIFF 10482 kb

Additional file 1: Table S1. of Residues of chlortetracycline, doxycycline and sulfadiazine-trimethoprim in intestinal content and feces of pigs due to cross-contamination of feed

Validation parameters for quantification of chlortetracycline (CTC), doxycycline (DOX), sulfadiazine (SDZ) and trimethoprim (TRIM) in pig feed and feces. (DOCX 15 kb

Data_Sheet_1_The Ontogeny of Cytochrome P450 Enzyme Activity and Protein Abundance in Conventional Pigs in Support of Preclinical Pediatric Drug Research.docx

<p>Since the implementation of several legislations to improve pediatric drug research, more pediatric clinical trials are being performed. In order to optimize these pediatric trials, adequate preclinical data are necessary, which are usually obtained by juvenile animal models. The growing piglet has been increasingly suggested as a potential animal model due to a high degree of anatomical and physiological similarities with humans. However, physiological data in pigs on the ontogeny of major organs involved in absorption, distribution, metabolism, and excretion of drugs are largely lacking. The aim of this study was to unravel the ontogeny of porcine hepatic drug metabolizing cytochrome P450 enzyme (CYP450) activities as well as protein abundances. Liver microsomes from 16 conventional pigs (8 males and 8 females) per age group: 2 days, 4 weeks, 8 weeks, and 6–7 months were prepared. Activity measurements were performed with substrates of major human CYP450 enzymes: midazolam (CYP3A), tolbutamide (CYP2C), and chlorzoxazone (CYP2E). Next, the hepatic scaling factor, microsomal protein per gram liver (MPPGL), was determined to correct for enzyme losses during the fractionation process. Finally, protein abundance was determined using proteomics and correlated with enzyme activity. No significant sex differences within each age category were observed in enzyme activity or MPPGL. The biotransformation rate of all three substrates increased with age, comparable with human maturation of CYP450 enzymes. The MPPGL decreased from birth till 8 weeks of age followed by an increase till 6–7 months of age. Significant sex differences in protein abundance were observed for CYP1A2, CYP2A19, CYP3A22, CYP4V2, CYP2C36, CYP2E_1, and CYP2E_2. Midazolam and tolbutamide are considered good substrates to evaluate porcine CYP3A/2C enzymes, respectively. However, chlorzoxazone is not advised to evaluate porcine CYP2E enzyme activity. The increase in biotransformation rate with age can be attributed to an increase in absolute amount of CYP450 proteins. Finally, developmental changes were observed regarding the involvement of specific CYP450 enzymes in the biotransformation of the different substrates.</p

Occurrence of mycotoxins (μg/kg) in ten commercially available racing pigeon feed samples.

<p>Occurrence of mycotoxins (μg/kg) in ten commercially available racing pigeon feed samples.</p

Main pharmacokinetic parameters of free carboplatin after intravenous administration (5 mg/kg BW) to chickens, ducks, pigeons and parakeets.

<p>Values are presented as mean ± SD.</p><p>AUC_0-t: area under the plasma concentration-time curve from time 0 to the last sample point with values above the limit of quantification, AUC_0-inf: area under the plasma concentration-time curve from time 0 to infinite, C₀: plasma concentration at time 0, k_e: elimination rate constant, T_1/2el: elimination half-life, Vd: volume of distribution, Cl: total body clearance.</p><p>Values within one parameter with a different superscript are statistically different at p < 0.05.</p><p>Main pharmacokinetic parameters of free carboplatin after intravenous administration (5 mg/kg BW) to chickens, ducks, pigeons and parakeets.</p

Plasma concentration-time profiles of free carboplatin in different avian species (chicken, duck, pigeon and parakeet) after intravenous administration of 5 mg carboplatin/kg body weight.

<p>Values are presented as mean + SD. The insert displays the chemical structure of carboplatin.</p