natgillin/translations-raw huggingface dataset:
Plasma radioactivity and closantel levels were monitored for up to 42 days after administration (non GLP).
Ravni radioaktivnosti in klozantela v plazmi so spremljali do 42 dni po dajanju (brez GLP).
The marketing authorisation holder argued further that, in practice, the CVMP recommendation would effectively mean that treatment of dairy animals with nitroxinil would not be an option and that this would, in turn, result in a lack of availability of efficacious treatment for fluke in dairy cattle.
Imetnik dovoljenja za promet je poudaril, da priporočilo Odbora dejansko pomeni, da v praksi zdravljenje molznic z nitroksinilom ne bo več mogoče, to pa bo povzročilo pomanjkanje učinkovitega zdravljenja metljavosti krav molznic.
Overall summary of the scientific evaluation of veterinary medicinal products containing active substances belonging to the class of flukicides for which no maximum residue limit has been established in milk and which are intended for use in ruminants producing milk for human consumption (see Annex I)
Splošni povzetek znanstvenega vrednotenja zdravil za uporabo v veterinarski medicini, ki vsebujejo zdravilne učinkovine proti metljajem, za katere ni bila določena mejna vrednost ostankov v mleku, in ki se uporabljajo pri prežvekovalcih, katerih mleko je namenjeno prehrani ljudi(glejte Prilogo I)
Based on these data it was concluded that triclabendazole residues in milk from animals treated 2 to 15 days before calving could be sufficiently high to result in total exposure of residues (in the foodbasket) over the ADI.
Zaključek na podlagi teh podatkov je, da so ravni ostankov triklabendazola v mleku pri živalih, zdravljenih od 2 do 15 dni pred telitvijo, tako visoke, da bo skupna izpostavljenost ostankom (v košarici živil) presegla vrednost ADI.
PharVet Ltd Station Road Bagenalstown Co. Carlow IRELAND
PharVet Ltd Station Road Bagenalstown Co. Carlow IRSKA
Belgium Chanelle Animal Health Limited 7 Rodney Street
Nizozemska Chanelle Animal Health Limited 7 Rodney Street
In order to establish the overall appropriateness of the product information with regard to the use in dairy animals the second active substance would need to be considered.
Da bi ugotovili splošno primernost informacij o zdravilu glede uporabe pri molznicah, je treba upoštevati tudi drugo zdravilno učinkovino.
Applicant/ Marketing Authorisation Holder
Imetnik dovoljenja za promet z zdravilom
The oral administration residue depletion study (study 1 above) demonstrated that milk from animals treated during the dry period between 45 and 56 days before calving may contain concentrations of closantel greater than 45 μg/l.
V študiji izločanja ostankov po peroralnem odmerku (zgoraj omenjena 1. študija) so dokazali, da mleko živali, zdravljenih v dobi presušitve od 45 do 56 dni pred telitvijo, lahko vsebuje klozantel v koncentraciji nad 45 μg/l.
S.P. Veterinaria S.A. Ctra Reus a Vinyols Km.4,1 43330 Riudoms (Tarragona) SPAIN
S.P. Veterinaria S.A. Ctra Reus a Vinyols Km.4,1 43330 Riudoms (Tarragona) ŠPANIJA
La Selva 135 17170 Amer (Gerona) SPAIN
17170 Amer (GeronaŠPANIJA
Kleermakersstraat 10 1191 JL Velserbroek THE NETHERLANDS
Kleermakersstraat 10 1191 JL
Vermifor Ecto Closantel
Vermifor Ecto klozantel
119 days
119 dni
299 days
299 dni
The time point at which the 95th percentile of the treated population would have plasma clorsulon concentrations below 53 μg/l with 95% confidence was calculated, using the Time-To-Safe-Concentration (TTSC) method, to be 12 days.
Časovna točka, ko bi imel 95. percentil zdravljene populacije s 95-odstotnim zaupanjem koncentracijo klorsulona v plazmi 53 µg/l, je bila izračunana z metodo časa do varne koncentracije (TTSC) in znaša 12 dni.
They have been used during the dry period with different precautionary measures including safety spans prior to calving,or lambing/kidding.
Uporabljajo se v dobi presušitve z različnimi previdnostnimi ukrepi, vključno z varnostnimi obdobji pred kotitvijo.
Ascacid Forte Rafoxanide Albendazole
Ascacid Forte rafoksanid albendazol
However, data are available on plasma closantel levels following subcutaneous administration (study 3) and, as indicated above, the level of closantel in milk can be considered to be safe when the level in plasma is below 2250 μg/l.
Vendar so na voljo podatki o ravneh klozantela v plazmi po subkutanem dajanju (3. študija) in (kot je prikazano zgoraj) se lahko raven klozantela v mleku šteje za varno, ko je raven klozantela v plazmi pod 2250 μg/l.
Pharmacokinetic study following oral administration of 14C-triclabendazole.
Farmakokinetična študija po enem peroralnem odmerku 14C-triklabendazola.
Following the CVMP opinion of 8 March 2012 recomending amendments of section 4.11 Withdrawal period(s) of the SPC for the veterinary medicinal products containing clorsulon, closantel, nitroxinil, rafoxanide or triclabendazole as a single active substance (see Annex I) and for the veterinary medicinal products administered as pour-on to cattle containing triclabendazole and moxidectin (see Annex I), on 23 March 2012, MERIAL notified the Agency of ther intention to request a re-examination of the CVMP opinion.
Po mnenju Odbora z dne 8. marca 2012, v katerem so bile priporočene spremembe poglavja 4.11 Karenca v povzetku glavnih značilnosti zdravil za uporabo v veterinarski medicini, ki vsebujejo klorsulon, klozantel, nitroksinil, rafoksanid ali triklabendazol kot edino zdravilno učinkovino (glejte Prilogo I), ter zdravil za uporabo v veterinarski medicini, ki se dajejo kot kožni poliv govedu in vsebujejo triklabendazol in moksidektin (glejte Prilogo I), je družba MERIAL dne 23. marca 2012 uradno obvestila agencijo, da bo zahtevala ponoven pregled mnenja Odbora.
Data are available on plasma closantel levels following oral administration (study 2 above) at the recommended dose.
Na voljo so podatki o ravneh klozantela v plazmi po peroralnem dajanju (zgoraj omenjena 2. študija) priporočenega odmerka.
• on the basis of the data provided it was considered that the risk associated with the absence of established MRLs in milk for clorsulon, closantel, nitroxinil, rafoxanide or triclabendazole may present a risk to public health;
• predloženi podatki kažejo, da odsotnost določenih mejnih vrednosti ostankov v mleku za klorsulon, klozantel, nitroksinil, rafoksanid in triklabendazol pomeni tveganje za javno zdravje;
Although 119 days was considered sufficient to allow for the depletion of residues of closantel to a safe concentration, as ivermectin was not within the scope of this referral and was therefore not evaluated, it was not possible to conclude whether 119 days would also allow residues of ivermectin to deplete to safe levels.
Čeprav se za izločitev ostankov klozantela na varno koncentracijo kot zadostno šteje 119 dni, ivermektin ni bil v obsegu te napotitve in se zato ni ocenjeval, kar pomeni, da ni bilo mogoče zaključiti, ali 119 dni omogoča izločitev tudi ostankov ivermektina na varne ravni.
However, as clorsulon was established as the marker residue in cattle tissues (CVMP Summary Report, 2008) and as the parent compound has been identified in bovine milk in a number of studies, clorsulon was also considered to be an appropriate marker residue for use in milk.
Ker je bil klorsulon določen kot označevalni ostanek v tkivih goveda (Zbirno poročilo CVMP, 2008), izvorna spojina pa je bila v več študijah odkrita v mleku goveda, se klorsulon šteje za primeren označevalni ostanek za uporabo v mleku.
Milk levels of closantel were measured for up to 84 days post treatment (GCP for animal phase and GLP for analytical phase).
Merili so ravni klozantela v mleku do 84 dni po zdravljenju (GCP za fazo na živalih in GLP za analitično fazo).
However, based on the results of study 1 reported above, a milk to plasma ratio of 0.3 was derived for the clorsulon.
Vendar je na podlagi rezultatov zgoraj omenjene 1. študije za klorsulon izpeljano razmerje med mlekom in plazmo, ki znaša 0,3.
Pour-on pour-on use
Pot uporabe
M g in amount safe µ equation 3 in which M = Molar mass (g/mol), A = Avogadro's number = 6.0 * 1023
M g in amount safe µ enačba 3, v kateri je M = molska masa (g/mol), A = Avogadrovo število = 6,0 * 1023 Rezultat enačbe 2 se vedno zaokroži na celo število dni.
A pharmacokinetic study was provided in which 5 lactating cows were administered a single subcutaneous injection of clorsulon.
Predložena je bila farmakokinetična študija, v kateri so petim kravam v laktaciji enkrat subkutano injicirali klorsulon.
Half-lives reported for closantel range between 10.8 and 24 days.
Razpolovna doba končnega izločanja klozantela je od 10,8 do 24 dni.
MRLs in milk have not been established for the flukicidal substances clorsulon, closantel, nitroxinil, rafoxanide and triclabendazole and therefore cannot be used in lactating animals.
Za mleko niso določene mejne vrednosti ostankov snovi proti metljajem: klorsulon, klozantel, nitroksinil, rafoksanid in triklabendazol, zato se ne smejo uporabljati za molznice.
Furthermore, use of the pharmacokinetic diffusion model based on pKa and protein binding is not possible in this case because information on the level of protein binding is sheep milk is not available (it is known that the binding to sheep milk proteins can deviate significantly from that to cattle milk proteins).
Poleg tega uporaba farmakokinetičnega difuzijskega modela na podlagi vrednosti pKa in vezave na beljakovine v tem primeru ni mogoča, ker podatkov o obsežnosti vezave na beljakovine v ovčjem mleku ni (znano pa je, da je lahko vezava na beljakovine v ovčjem mleku bistveno drugačna kot na beljakovine v kravjem mleku).
Flukiver Bovis Closantel
Flukiver Bovis klozantel
SEPONVER PLUS (75 mg + 50 mg) suspensão oral para ovinos
SEPONVER PLUS (75 mg + 50 mg) suspensão oral para ovinos klozantel mebendazol
Scientific conclusions and grounds for amendment of the summaries of product characteristics and package leaflets
Znanstveni zaključki in podlaga za dopolnilo povzetka glavnih značilnosti zdravila in navodila za uporabo
MERIAL's grounds for requesting a re-examination of the CVMP opinion focused on the fact that the results of a study using its marketed nitroxinil containing solution for injection indicate that by 71 days after administration of the product to dry cattle, residues in milk were at or below 20 µg/l, which the CVMP concluded to be a level of residues in milk that would not represent a consumer safety concern.
Obrazložitev zahtevka družbe MERIAL po ponovnem pregledu mnenja Odbora je osredotočena na dejstvo, da rezultati študije raztopine za injiciranje, ki vsebuje nitroksinil in jo omenjena družba daje v promet, kažejo, da po 71 dneh po uporabi zdravila pri govedu v dobi presušitve ravni ostankov v mleku niso bile višje od ravni 20 µg/l, za katero je Odbor presodil, da je raven ostankov v mleku, ki ne pomeni varnostnega tveganja za potrošnika.
However, as closantel was established as the marker residue in cattle tissues (CVMP Summary Report, 1996) and as the substance is known to undergo only limited metabolism in vivo, closantel was also considered to be an appropriate marker residue for use in milk.
Ker je bil klozantel določen kot označevalni ostanek v tkivih goveda (Zbirno poročilo CVMP, 1996), za spojino pa je znano, da se in vivo le malo presnovi, se tudi klozantel šteje za primeren označevalni ostanek za uporabo v mleku.
In the absence of data in milk, any estimation of a marker to total residues ratio should be suitably conservative.
Ker podatkov za mleko ni, morajo biti vse ocene razmerja označevalca proti skupnim ostankom primerno konservativne.
Leijsendwarsstraat 26 4901 PG, Oosterhout THE NETHERLANDS
4901 PG, Oosterhout NIZOZEMSKA
A tissue residue depletion including data on plasma clorsulon levels was provided, in which forty cattle were administered single subcutaneous injections of 2 mg/kg bw clorsulon.
Predložena je bila študija izločanja ostankov iz tkiva, ki je vključevala podatke o plazemskih ravneh klorsulona, v kateri so štiridesetim kravam enkrat subkutano injicirali klorsulon v odmerku 2 mg/kg TM.
The evaluation concludes that use of these substances during the non-lactating period could lead to residue levels in milk that are sufficient to result in consumer exposure over the ADI.
Zaključek vrednotenja je, da uporaba teh snovi zunaj obdobja laktacije lahko privede do ravni ostankov v mleku, ki so dovolj visoke, da izpostavljenost potrošnika presega vrednost ADI.
Although 12 days was considered sufficient to allow for the depletion of residues of clorsulon to a safe concentration, as ivermectin was not within the scope of this referral and was therefore not evaluated, it was not possible to conclude whether 12 days would also allow residues of ivermectin to deplete to safe levels.
Čeprav se za izločitev ostankov klorsulona na varno koncentracijo kot zadostno šteje 12 dni, ivermektin ni bil v obsegu te napotitve in se zato ni vrednotil, kar pomeni, da ni bilo mogoče zaključiti, ali 12 dni omogoča izločitev tudi ostankov ivermektina na varne ravni.
The time required for closantel levels in plasma to deplete to 2250 μg/l following pour-on application to animals at the same time point was calculated to be 119 days.
Čas, potreben za upad plazemskih ravni klozantela na 2250 μg/l po dajanju kožnega poliva, je po izračunu približno 119 dni.
Ivermectin does also not have a MRL in milk.
Za ivermektin ravno tako ni določena mejna vrednost ostankov v mleku.
Residue depletion study following a single oral administration of 10 mg/kg bw closantel to 11 pregnant cows 40 to 45 days before expected calving.
Študija izločanja ostankov po enem peroralnem odmerku klozantela 10 mg/kg TM 11 brejim kravam od 40 do 45 dni pred pričakovano telitvijo.
Flukiver 50mg/ml Ijektionslösung für Rinder
Flukiver 50mg/ml Ijektionslösung für Rinder klozantel
This referral sought to determine whether this use of these substances would result in residues in milk that, when combined with residues of these substances in other food commodities, could result in consumer exposure over the ADI.
Cilj te napotitve je bil ugotoviti, ali uporaba teh snovi privede do ostankov v mleku, ki lahko v kombinaciji z ostanki istih snovi v drugih živilih privedejo do izpostavljenosti potrošnika, ki presega vrednost ADI.
Pharmacokinetic study in which 5 heifers and 4 steers were administered a single (oral) dose 10 mg/kg bw 14C-labelled closantel by intubation into the rumen.
Farmakokinetična študija na 5 telicah in 4 volih, ki so prejeli en (peroralni) odmerek s 14C označenega klozantela 10 mg/kg TM skozi intubacijo v rumen.
Flukiver 50 mg/ml, oplossing voor injectie
Flukiver 50 mg/ml, oplossing voor injectie klozantel
• The scope of the referral was to determine whether measures are necessary to ensure that the use during the non-lactating period, of veterinary medicinal products containing flukicidal substances for which maximum residue limits have not been established in milk would not lead to residues in milk that, combined with residues of these flukicidal substances from other foodstuffs, would result in consumer exposure exceeding the exceeding the acceptable daily intake;
• obseg te napotitve je bil ugotoviti, ali so potrebni ukrepi, s katerimi se zagotovi, da uporaba zdravil za uporabo v veterinarski medicini, ki vsebujejo zdravilne učinkovine proti metljajem, za katere ni bila določena mejna vrednost ostankov v mleku, zunaj obdobja laktacije ne povzroči ostankov v mleku, ki bi v kombinaciji z ostanki teh snovi proti metljajem iz drugih živil privedle do izpostavljenosti potrošnikov, ki presega dopustni dnevni vnos;
D-48308 Senden-Bösensell GERMANY
D-48308 SendenBösensellNEMČIJA
It is concluded that consumption of milk from animals treated at the same time point with pour-on closantel during the first half of their pregnancy, would not lead to a total consumer intake exceeding the ADI.
Sledi zaključek, da zaužitje mleka živali, zdravljenih z dajanjem kožnega poliva v prvi polovici brejosti, pri potrošniku s skupnim vnosom ne povzroči preseganja vrednosti ADI.
As the scope of the current referral was restricted to the evaluation of flukicidal substances only, the depletion of the second active substance was not evaluated and it was not possible to conclude whether the time spans indicated above would also allow residues of the second active substance to deplete to safe levels.
Ker je obseg te napotitve omejen samo na vrednotenje snovi proti metljajem, izločanje druge zdravilne učinkovine ni bilo ovrednoteno, zato ni bilo mogoče zaključiti, ali zgoraj prikazani časovni presledki omogočajo upad tudi druge zdravilne učinkovine na varno raven.
Biotransformation and excretion study following single oral administration of rafoxanide 131I-rafoxanide to 2 cattle and 2 sheep.
Študija biotransformacije in izločanja na 2 kravah in 2 ovcah po enem peroralnem odmerku 131I-rafoksanida.
• the CVMP considered that the overall benefit-risk balance is positive for the products containing clorsulon, closantel, nitroxinil, rafoxanide or triclabendazole as single active substances, and for the veterinary medicinal products administered as pour-on containing triclabendazole and moxidectin, subject to inclusion of adequate instructions and warning sentences concerning the use in dairy cattle in the product information;
• Odbor je menil, da je skupno razmerje med koristmi in tveganjem pozitivno za vsa zdravila, ki vsebujejo klorsulon, klozantel, nitroksinil, rafoksanid ali triklabendazol kot edino zdravilno učinkovino, ter za zdravila za uporabo v veterinarski medicini, ki se dajejo kot kožni poliv in vsebujejo triklabendazol in moksidektin, če se v informacije o zdravilih vnese ustrezno navodilo za uporabo pri molznicah;
Indeed, it should be noted that the derivation of a withdrawal period uses established MRLs as the starting point.
Vsekakor je treba izpostaviti, da je karenca v izhodišču izpeljana iz uveljavljenih mejnih vrednosti ostankov.
Based on this it was estimated that the safe level in milk (6 µg/l) would occur when the plasma concentration of rafoxanide is 0.18 µg/ml.
Na podlagi tega do ocenjene varne ravni v mleku (6 µg/l) pride, ko je koncentracija rafoksanida v plazmi 0,18 µg/ml.
Flukiver Bovis 50 mg/ml Solution for Injection
Flukiver Bovis 50 mg/ml Solution for Injection klozantel
Pharmacokinetic study in which 16 male cattle were administered single subcutaneous injections of one of two closantel formulations, at doses of 5 mg/kg bw.
Farmakokinetična študija na 16 bikih, ki so prejeli eno subkutano injekcijo ene od dveh formulacij klozantela v odmerku 5 mg/kg TM.
Endoex Inyectable
Endoex Inyectable klozantel
Fasinex 240, 24% w/v Oral Suspension for Cattle
Fasinex 240, 24% w/v Oral Suspension for Cattle triklabendazol
Flukiver 5% Closantel
Flukiver 5% klozantel
As the metabolism of clorsulon in milk has not been characterised, any estimation of a marker to total residues ratio should be conservative.
Ker presnova klorsulona v mleku ni preučena, morajo biti vse ocene razmerja označevalca proti skupnim ostankom konservativne.
Using the longest reported figure of 16.6 days, a molecular weight of 626, a dose of 7.5 mg/kg bw, and a body weight of 50kg, the time needed to ensure a total residue burden equal to a safe number of molecules in 1.5 l milk was calculated to be 272 days which, for the purposes of this referral, can be rounded up to 1 year.
Če uporabimo največjo objavljeno številko 16,6 dneva, molekulsko maso 626, odmerek 7,5 mg/kg TM in telesno maso 50 kg, je izračunani čas, potreben, da je skupno breme ostankov enako varnemu številu molekul v 1,5 l mleka, 272 dni, kar lahko za namen te napotitve zaokrožimo na 1 leto.
Virbamec F. oplossing voor injectie
Virbamec F. oplossing voor injectie klorsulon ivermektin
Based on this it was estimated that the safe level in milk (45 µg/l) would occur when the plasma concentration of closantel is 2250 µg/l.
Na podlagi tega se ocenjuje, da je varna raven v mleku (45 µg/l) dosežena, ko je koncentracija klozantela v plazmi 2250 µg/l.
Edifício Suécia III, Piso 1 2794-044 Carnaxide PORTUGAL
2794-044 Carnaxide PORTUGALSKA
Trodax 34% w/v Solution for Injection
Trodax 34% w/v Solution for Injection nitroksinil govedo, ovce
Luxembourg Merial Belgium S.A. Boulevard Sylvain Dupuis 243 B-1070 Bruxelles
Luksemburg Merial Belgium S.A. Boulevard Sylvain Dupuis 243
Based on this it was estimated that the safe level in milk (16 µg/l) would occur when the plasma concentration of clorsulon is 53 µg/l.
Na podlagi tega do ocenjene varne ravni v mleku (16 µg/l) pride, ko je koncentracija klorsulona v plazmi 53 µg/l.
It was therefore considered appropriate to apply the marker to total residues ratio of 0.7, established for bovine fat, to milk as milk has a high fat content and limited metabolic activity (marker to total residues ratios established for bovine liver, kidney and muscle are 0.10, 0.80 and 1.00, respectively).
Zato je bilo primerno za mleko uporabiti razmerje označevalca proti skupnim ostankom 0,7, ki je določeno za maščobo govedi, saj ima mleko visoko vsebnost maščobe in majhno presnovno aktivnost (razmerje označevalca proti skupnim ostankom je pri govedu v jetrih 0,10, v ledvicah 0,80 in v mišicah 1,00).
Plasma closantel levels were monitored for up to 1488 hours after administration (GLP study).
Plazemske ravni klozantela so spremljali do 1488 ur po odmerjanju (GLP študija).
Schippers Europe B.V. Rond Deel 12
Nizozemska Schippers Europe B.V.
B-2340 Beerse
B-2340 BeerseBELGIJA
Flukiver 5% w/v Oral Suspension
Flukiver 5% w/v Oral Suspension klozantel
Do not use during 2nd half of gestation period
Ne uporabite v drugi polovici brejosti klozantel
Using this value, a molecular weight of 359.66, a dose of 10 mg/kg bw, and a body weight of 50 kg, the time needed to ensure a total residue burden equal to a safe number of molecules in 1.5 l milk was calculated to be 359 days.
Če uporabimo to vrednost, molekulsko maso 359,66, odmerek 10 mg/kg TM in telesno maso 50 kg, je čas, potreben, da je skupno breme ostankov enako varnemu številu molekul v 1,5 l mleka, 359 dni.
the CVMP has recommended variations of the marketing authorisations for the veterinary medicinal products containing clorsulon, closantel, nitroxinil, rafoxanide or triclabendazole as single active substances, and for the triclabendazole-containing veterinary medicinal products administered as pouron (see Annex I) in order to amend the Summaries of Product Characteristics and package leaflets in line with recommended changes in the product information as set out in Annex III.
je Odbor priporočil spremembe dovoljenj za promet z zdravili za zdravila za uporabo v veterinarski medicini, ki vsebujejo klorsulon, klozantel, nitroksinil, rafoksanid ali triklabendazol kot edino zdravilno učinkovino, ter za zdravila za uporabo v veterinarski medicini, ki vsebujejo triklabendazol in se dajejo kot kožni poliv (glejte Prilogo I), da se spremenijo povzetki glavnih značilnosti zdravila in navodila za uporabo skladno s priporočenimi spremembami informacij o zdravilu, navedenimi v Prilogi III.
Grounds for amendment of the summaries of product characteristics and package leaflets
Razlogi za spremembo povzetkov glavnih značilnosti zdravila in navodil za uporabo
Fasimec Duo S 0.1%/5% Oral Suspension for Sheep
Fasimec Duo S 0.1%/5% Oral Suspension for Sheep triklabendazol ivermektin
Endoex Oral
Endoex Oral klozantel
Residue study in milk following oral administration of triclabendazole to cows around two months before calving.
Študija ostankov v mleku po peroralnem dajanju triklabendazola kravam približno dva meseca pred telitvijo.
In the remainder of this opinion this is referred to as ‘the time needed to ensure a total residue burden equal to a safe number of molecules in 1.5 l milk'.
V nadaljevanju tega mnenja se na to nanaša izraz „čas, potreben, da je skupno breme ostankov enako varnemu številu molekul v 1,5 l mleka“.
Residues of triclabendazole in goats' milk
Ostanki triklabendazola v kozjem mleku