Pyrrolizidine alkaloids in commercial feedstuffs for horses.

BACKGROUND: Pyrrolizidine alkaloids are secondary plant metabolites with hepatotoxic effect in humans and several animal species. In recent studies, foods such as herbal teas and honey have been found to be contaminated with pyrrolizidine alkaloids. OBJECTIVES: The aim of this study was to identify and assess pyrrolizidine alkaloids in compound feeds manufactured for horses and containing either alfalfa or a blend of herbs. METHODS: Forty-eight feed products for horses were included in the study. The feedstuffs were analysed for 28 selected pyrrolizidine alkaloids by liquid chromatography-mass spectrometry. The concentrations of the individual pyrrolizidine alkaloids were summed to calculate the total pyrrolizidine alkaloid content. RESULTS: In 7 of 48 samples, pyrrolizidine alkaloid concentrations were below the limit of quantification of 1-5 µg/kg. The median of 41 out of 48 samples was 58 µg/kg, and the 25 and 75th percentiles were 8 and 151 µg/kg. The highest observed pyrrolizidine alkaloid concentrations, 1306 and 1222 µg/kg, were found in two alfalfa-based feed products, followed by 836 µg/kg in an herb-containing feed product. Lycopsamine, seneciphylline, seneciphylline-N-oxide, senecionine and senecionine-N-oxide were the most frequently detected alkaloids. MAIN LIMITATIONS: Risk assessment was based on no-observed-adverse-effect-level for pyrrolizidine alkaloids in rats and humans. The specific susceptibility of horses to pyrrolizidine alkaloids remains unknown. CONCLUSIONS: According to our risk assessment, pyrrolizidine alkaloid contamination should be limited to <90 µg/kg in equine compound feeds. We showed a high rate of pyrrolizidine alkaloids contamination in feed products for horses. In 43% of the analysed samples, pyrrolizidine alkaloid levels exceeded the calculated maximum tolerable levels. There is a need to introduce measures to reduce pyrrolizidine contamination in equine feedstuffs. The Summary is available in Portuguese - see Supporting Information.

[New drugs for horses and production animals in 2014]. / Neue Arzneimittel für Pferde und landwirtschaftliche Nutztiere 2014.

In 2014, no new active pharmaceutical ingredients were released on the German market for horses and food producing animals. One established veterinary active pharmaceutical ingredient is avaibable for an additional species. The analgetic buprenorphine (Buprenodale® Multidose) has additionally been authorized for horses. Furthermore, four new preparations with a new pharmaceutical form, one drug with a new formulation, new galenics and a new indication, respectively, have recently been released to the market. Furthermore, the prostaglandin F2α analoque luprostiol is available again.

[New drugs for small animals in 2014]. / Neue Arzneimittel für Kleintiere 2014.

In 2014, six active pharmaceutical ingredients were released on the German market for small animals. Those are the ektoparasiticide of the isoxazoline group afoxolaner (NexGard®) and fluralaner (Bravecto®) and the neonicotinoid dinotefuran (Vectra 3D, Vectra Felis), the antidiabetic protamine zinc insulin of human origin (ProZinc®), the antifungal agent ketoconazole (Fugazid®) as well as the cytostatic drug oclacitinib (Apoquel®). Two substances were authorized for an additional species. The antiparasiticide eprinomectin and the antibiotic clindamycin were also authorized for use in cats. In addition, two active pharmaceutical ingredients, which were approved 2014 for use in human medicine and are of potential interest to veterinary medicine, are discussed. These are the antihypertensive drug riociguat and the urological substance mirabegron.

[Alimentary intake of opioid alkaloids by horses. Hazards due to poppy-containing feeds]. / Alimentäre Aufnahme von Opioid-Alkaloiden durch Pferde. Gefahren durch mohnhaltige Futtermittel.

Opioid alkaloids were identified in the urine of horses during an anti-doping control and in a case of intoxication. In both cases, it was suspected that the horses had ingested poppy-contaminated feed. To verify this suspicion, possible opioid alkaloid sources in Germany were identified through a literature research. Additionally, the contaminated feed was botanically and chemically analysed. The results indicated that both cases were most probably caused by the poppy in the feed. This highlights the previously underestimated risk of an intake of poppy-contaminated feed in horses. Recommendations are formulated for the prevention of positive doping-test results and intoxications by poppy-contaminated feeds in horses. Furthermore, a threshold for morphine in urine samples in competing horses is proposed.

[New drugs for horses and production animals in 2013]. / Neue Arzneimittel für Pferde und landwirtschaftliche Nutztiere 2013.

In 2013, only one newly developed active pharmaceutical ingredient for horses and food-producing animals was released on the German market for veterinary drug products. The ionophore monensin from the group of polyether antibiotics is now available as an orally administered continuous release intraruminal device for cattle (Kexxtone®). Furthermore, two established veterinary active pharmaceutical ingredients are available for additional species: The antibiotic amoxicillin (Suramox®) is also authorized for ducks and turkeys and the dissociative anesthetic ketamine is now authorized for sheep, goats and dairy cattle. Additionally, one veterinary drug with a new pharmaceutical form as well as one product with a new strength have been launched on the market for veterinary drugs for horses and food producing animals.

[New drugs for small animals in 2013]. / Neue Arzneimittel für Kleintiere 2013.

In 2013, four active pharmaceutical ingredients were released on the German market for small animals. Those are the recombinant human bone morphogenetic protein-2 dibotermin alfa (TruScient®), the ectoparasiticide of the oxadiazine group indoxacarb (Activyl®), the antiepileptic imepitoin (Pexion®) and the angiotensin-II1-receptor antagonist telmisartan (Semintra®). One substance was authorized for an additional species. The prolactin antagonist cabergoline is now also authorized for use in cats. In addition, three active pharmaceutical ingredients, which were approved in 2013 for use in human medicine and are of potential interest to veterinary medicine, are discussed. These are the antineoplastic ingredients dabrafenib, enzalutamide and vismodegib.

[Obtaining sturgeon spawn in accordance with the German Pharmaceuticals Act]. / Laichgewinnung bei Stören aus arzneimittelrechtlicher Sicht.

Obtaining sturgeon spawn in aquaculture is carried out with different objectives. Sturgeons are increasingly used for ornamental purposes or to serve as food. Previously, sturgeon roe was obtained primarily by surgical opening of the abdomen or during slaughter. Recently, in aquaculture roe has been increasingly produced by stripping off the eggs. In this new method it is necessary to synchronize spawn production by stimulating the fish through hormone usage. Therefore, the complete egg package can be taken from the fish, which avoids resorption disorders. This article discusses how this method can be evaluated from the perspective of drug law.

[New drugs for small animals in 2012]. / Neue Arzneimittel für Kleintiere 2012.

In 2012, three active pharmaceutical ingredients were released on the German market for small animals. These are the anti-thyroid Carbimazole (Vidalta®), the opium-derived analgesic Fentanyl (Fentadon®) and the antiepileptic Potassium Bromide (Libromide®). One substance was authorized for an additional species. The insecticide Flumethrin in combination with Imidacloprid is now also authorized for use in cats. Furthermore, this preparation includes an interesting new pharmaceutical form for dogs and cats and a new combination of active pharmaceutical ingredients for dogs. In addition, three active pharmaceutical ingredients with approval for use in human medicine, which are of potential interest to veterinary medicine, entered the market in 2012. These are the antidiabetic Dapagliflozin, the antiepileptic Perampanel and the Somatostatin-analog Pasireotide.

[New drugs for horses and production animals in 2012]. / Neue Arzneimittel für Pferde und landwirtschaftliche Nutztiere 2012.

In 2012, two newly developed active pharmaceutical ingredients for horses and food producing animals were released on the German market for veterinary drug products. Those are the parenterally applicable first generation cephalosporin Cefalonium (Cepravin®) and the nonsteroidal anti-inflammatory drug Suxibuzone (Danilon®). Furthermore, one established veterinary active pharmaceutical ingredient is applicable to additional species: The anticoccidial Amprolium (Eimeryl®) has again been authorized for chicken and turkeys. Additionally, two veterinary drugs with a new formulation as well as three products with a new strength and one product with a new indication have recently been released to the veterinary drugs market for horses and food producing animals.

[New drugs for small animals in 2011]. / Neue Arzneimittel für Kleintiere 2011.

In 2011, nine active pharmaceutical ingredients were released on the German market for small animals. Those are the cyclooxygenase-2-inhibitor Cimicoxib (Cimalgex®), the opium-derived analgesic Methadone (Comfortan®), the antiemetic Metoclopramide (Emeprid®), the corticosteroid Mometasone furoate in combination with the antifungal agent Posaconazole (Posatex®), the fluorchinolone-antibiotic Pradofloxacin (Veraflox®), the insecticide Spinosad (Comfortis®), the cytostatic Toceranib (Palladia®) and the vitamin Phytomenadione (Vitamin K1 Laboratoire TVM). Two additional substances were authorized for additional species. The tetracycline-antibiotic Doxycycline is now available for carrier pigeons and the anticoccidial Toltrazuril in combination with Emodepside is likewise authorized for dogs. Furthermore, one new preparation with an interesting new pharmaceutical form and two products with a new strength were added to the market for small animals. In addition, four active pharmaceutical ingredients with approval for use in human medicine, which are of potential interest to veterinary medicine, entered the market in 2011. Those are the antiepileptic Retigabine, the ophthalmic Bromfenac, the psychotropic drug Dexamfetamine and the cytostatic Eribulin.

[New drugs for horses and production animals in 2011]. / Neue Arzneimittel für Pferde und landwirtschaftliche Nutztiere 2011.

In 2011, three newly developed active pharmaceutical ingredients for horses and food producing animals were released on the German market for veterinary drug products. Two of these new products represent different drug classes of antibiotics, the polypeptide antibiotic Bacitracin (Bacivet™) and the macrolide antibiotic Clorsulon (Levatum®). The third product represents an anticestodal antiparasitic (Tildipirosin, Zuprevo®). Furthermore, three established veterinary active pharmaceutical ingredients were modified to allow their application for additional species. Thus the nonsteroidal anti-inflammatory drug sodium salicylate is now additionally authorised for turkeys and both the macrolide antibiotic Tilmicosin and the anticoccidial drug Toltrazuril are currently available for sheep. Additionally, two veterinary drugs with a new formulation as well as a veterinary drug for horses and food producing animals with a resourceful new combination of active pharmaceutical ingredients have recently been released.

[New drugs for horses and production animals in 2010]. / Neue Arzneimittel für Pferde und landwirtschaftliche Nutztiere 2010.

In 2010, three new active pharmaceutical ingredients were released on the German market for horses and food-producing animals. These were gamithromycin (Zactran®), a new macrolide antibiotic, Monepantel (Zolvix®), a broad spectrum anthelmintic with a novel mechanism, and Pergolide (Prascend®), the first dopamine receptor agonist for animals. Two substances have been approved for additional species. The tetracycline antibiotic doxycycline is now also authorized for turkeys and the nonsteroidal anti-inflammatory drug firocoxib from the group of cyclo-oxygenase-2 (COX-2) inhibitors is now available for horses. Furthermore, four new preparations with an interesting new pharmaceutical form, one drug with a new formulation and two drugs, which are interesting because of other criteria, were added to the market for horses and food producing animals.

[New drugs for small animals in 2010]. / Neue Arzneimittel für Kleintiere 2010.

In 2010, no active pharmaceutical ingredients were released on the German market for small animals. Furthermore, no additional substances were authorized for additional species. Only one drug with an interesting new pharmaceutical form, two products with a new strength and one drug, which is interesting because of other criteria, were added to the market for small animals. In addition, nine active pharmaceutical ingredients with approval for use in human medicine, which are of potential interest for veterinary medicine, entered the market in 2010. Those are the analgesic Tapentadol, the antiallergicum Bilastine, the antiarrhythmics Dronedarone and Vernakalant, the antihaemorrhagic Eltrombopag, the bronchodilator Roflumilast, the hormone Corifollitropin alfa, the laxative Prucalopride and the cytostatic Mifamurtide.

[New drugs for small animals in 2009]. / Neue Arzneimittel für Kleintiere 2009.

In 2009, five active pharmaceutical ingredients were released on the German market for small animals. Those are the analgesic Buprenorphin (Buprenovet®), the cytostatic Masitinib (Masivet®), the antiepileptic Phenobarbital (Phenoleptil®) and the cyclooxygenase-2-inhibitors Mavacoxib (Trocoxil®) and Robenacoxib (Onsior®). Six additional substances were authorized for additional species. Benazepril, Cefalexin, Ivermectin und Ramipril are now available for cats, Emodepsid in combination with Praziquantel is likewise authorized for dogs and the combination Imidaclopird + Moxidectin is now also available for ferrets. Furthermore, two new preparations with an interesting new pharmaceutical form were added to the market for small animals. In addition seven active pharmaceutical ingredients with approval for use in human medicine which are of potential interest for veterinary medicine, entered the market in 2009. Those are the antiepileptic Eslicarbazepinacetat, the antihemorrhagic Romiplostim, the anticoagulant Prasugrel, the vasopressin-antagonist Tolvaptan as well as the cytostatics Azacitidin, Plerixafor and Vinflunin.