natgillin/translations-raw huggingface dataset:
The benefit of atosiban in these subgroups is therefore uncertain.
Koristi atosibana v teh podskupinah so zato negotove.
Re-treatment:
Ponovno zdravljenje:
Date of first authorisation: 20 January 2000 Date of latest renewal: 20 January 2010
Datum prve pridobitve dovoljenja za promet: 20.januar 2000 Datum zadnjega podaljšanja dovoljenja za promet: 20.januar 2010
It is not known whether M1 accumulates in tissues.
Ni znano, ali se M1 kopiči v tkivih.
For intravenous use only.
Le za intravensko uporabo.
- if you are more than 33 weeks pregnant.
- Če ste noseči več kot 33 tednov.
- if you are between 24 and 27 weeks pregnant.
- Če ste med 24. in 27. tednom nosečnosti.
• Whenever the risk management system is modified, especially as the result of new informationbeing received that may lead to a significant change to the benefit/risk profile or as the result ofan important (pharmacovigilance or risk minimisation) milestone being reached.
• ob vsakršni spremembi sistema za obvladovanje tveganj, zlasti kadar je tovrstna sprememba posledica prejema novih informacij, ki lahko privedejo do znatne spremembe razmerja med koristmi in tveganji, ali kadar je ta sprememba posledica tega, da je bil dosežen pomemben mejnik (farmakovigilančni ali povezan z zmanjševanjem tveganja).
- if you are allergic to atosiban or any of the other ingredients of this medicine (listed in section 6).
- Če ste alergični na atosiban ali katerokoli sestavino tega zdravila (navedeno v poglavju 6).
Do not use Tractocile: - if you are less than 24 weeks pregnant.
Zdravila Tractocile ne smete prejeti: - Če ste noseči manj kot 24 tednov.
Once the bolus has been injected, proceed with the infusion.
Ko je bolus injiciran, nadaljujte z infuzijo.
The highest atosiban subcutaneous dose not producing any adverse effects was approximately two times the therapeutic human dose.
Največji subkutani odmerek atosibana, ki ni povzročil nobenih neželenih učinkov, je bil približno dvakrat večji od terapevtskega odmerka pri človeku.
This permits the continued independent control of the rate of infusion.
To omogoča stalen neodvisen nadzor nad hitrostjo infundiranja.
Tractocile must not be used in the following conditions:
Zdravila Tractocile se ne sme uporabljati v naslednjih primerih:
There is no known specific treatment in case of an overdose.
Specifično zdravljenje v primeru prevelikega odmerjanja ni znano.
The ratios of the main metabolite M1 (des-(Orn
Razmerje med koncentracijo glavnega presnovka M1 (des-(Orn
Tell your doctor, midwife or pharmacist if you are taking, have recently taken or might take any other medicines.
Obvestite svojega zdravnika, babico ali farmacevta, če jemljete, ste pred kratkim jemali ali pa boste morda začeli jemati katerokoli drugo zdravilo.
• Periodic Safety Update Reports requirements for submission of periodic safety update reports for this medicinal product are set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any subsequent updates published on the European medicines web-portal.
Zahteve glede predložitve rednega posodobljenega poročila o varnosti zdravila za to zdravilo so določene v seznamu referenčnih datumov EU (seznamu EURD), opredeljenem v členu 107c(7) Direktive 2001/83/ES, in vseh kasnejših posodobitvah, objavljenih na evropskem spletnem portalu o zdravilih.
- if your waters have broken (premature rupture of your membranes) and you have completed 30 weeks of your pregnancy or more.
- Če vam je odtekla voda (predčasni razpok plodovega mehurja), noseči pa ste že 30 tednov ali dlje.
In case of intrauterine growth retardation, the decision to continue or reinitiate the administration of Tractocile depends on the assessment of fetal maturity.
V primeru intrauterinega zavrtja rasti je odločitev za nadaljevanje ali ponoven začetek uporabe zdravila Tractocile odvisna od ocene zrelosti ploda.
- high blood sugar
- Zvišana vrednost krvnega sladkorja.
The most commonly reported adverse reaction in the mother is nausea (14 %).
Pri materah so najpogosteje poročali o siljenju na bruhanje (14 %).
Re-treatment with Tractocile is possible, but there is only limited clinical experience available with multiple re-treatments, up to 3 re-treatments (see section 4.2).
Ponovno zdravljenje z zdravilom Tractocile je mogoče, vendar so klinične izkušnje z večkratnimi ponovitvami omejene (do 3 ponovitve zdravljenja) (glejte poglavje 4.2).
Few cases of atosiban overdosing were reported, they occurred without any specific signs or symptoms.
Opisanih je bilo nekaj primerov prevelikega odmerjanja atosibana; potekali so brez specifičnih znakov ali simptomov.
Atosiban is found in only small quantities in urine, its urinary concentration is about 50 times lower than that of M1.
Atosiban se v urinu pojavi le v majhni količini; njegova koncentracija v urinu je približno 50-krat manjša od koncentracije M1.
- if you have or could have an infection of your womb (uterus).
- Če imate ali bi lahko imeli okužbo maternice (uterusa).
Tractocile will be given to you in a hospital by a doctor, nurse or midwife.
Zdravilo Tractocile vam bo v bolnišnici dal zdravnik, medicinska sestra ali babica.
Signs may include feeling dizzy or light-headed.
Znaki lahko vključujejo omotico ali vrtoglavico.
Tractocile should not be mixed with other medicinal products in the infusion bag.
Zdravila Tractocile ne smete mešati z drugimi zdravili v isti infuzijski vrečki.
Pharmacotherapeutic group: Other gynecologicals, ATC code: G02CX01
Farmakoterapevtska skupina: druga ginekološka zdravila, oznaka ATC: G02CX01
Admission to a neonatal intensive care unit (NICU) was similar for both treatment groups (approximately 30%), as was length of stay and ventilation therapy.
Delež sprejemov v neonatalno enoto za intenzivno nego je bil v obeh zdravljenih skupinah podoben (približno 30 %), prav tako trajanje bivanja in ventilacijska terapija.
The frequency of adverse reactions listed below is defined using the following convention: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000).
Pogostnost v nadaljevanju navedenih neželenih učinkov je navedena v skladu z naslednjim dogovorom: zelo pogosti (≥ 1/10), pogosti (≥ 1/100 do < 1/10), občasni (≥ 1/1.000 do < 1/100), redki (≥ 1/10.000 do < 1/1.000).
The clearance, volume of distribution and half-life were found to be independent of the dose.
Očistek, volumen porazdelitve in razpolovni čas niso odvisni od odmerka.
For women with a gestational age greater than 24 weeks there was no difference in mortality rate (1.7% in the placebo group and 1.5% in the atosiban group).
Pri ženskah z gestacijsko starostjo nad 24 tednov ni bilo razlik v umrljivosti (1,7 % v skupini s placebom in 1,5 % v skupini z atosibanom).
The safety and efficacy of Tractocile in pregnant women aged less than 18 years have not been established.
Varnost in učinkovitost zdravila Tractocile pri nosečnicah, starih manj kot 18 let, nista bili dokazani.
If other medicinal products need to be given intravenously at the same time, the intravenous cannula can be shared or another site of intravenous administration can be used.
Če je sočasno treba intravensko aplicirati tudi druga zdravila, je mogoče uporabiti isto intravensko kanilo ali pa intravensko aplikacijo opraviti na drugem mestu.
Interaction studies have been performed with labetalol and betamethasone in healthy, female volunteers.
Izvedene so bile študije medsebojnega delovanja z labetalolom in betametazonom pri zdravih prostovoljkah.
8]-oxytocin) which is a competitive antagonist of human oxytocin at receptor level.
4,Orn oksitocin), ki je kompetitivni antagonist človeškega oksitocina na receptorski ravni.
What Tractocile is and what it is used for
Kaj je zdravilo Tractocile in za kaj ga uporabljamo
Plasma protein binding of atosiban is 46 to 48% in pregnant women.
Pri nosečnicah se od 46 do 48 % atosibana veže na beljakovine v plazmi.
Treatment with Tractocile should be initiated and maintained by a physician experienced in the treatment of pre-term labour.
Zdravljenje z zdravilom Tractocile mora uvesti in voditi zdravnik, ki ima izkušnje z zdravljenjem prezgodnjega poroda.
Tractocile contains atosiban (INN), a synthetic peptide ([Mpa
Zdravilo Tractocile vsebuje atosiban (INN), sintetičen peptid ([Mpa
- if you have kidney or liver problems.
- Če imate težave z ledvicami ali jetri.
Most of the treatment failures in CAP-001 were caused by poor tolerability.
V študijah CAP-001 je bilo neuspešno zdravljenje večinoma posledica slabega prenašanja zdravila.
Secondary endpoints: secondary efficacy parameters included the proportion of women remaining undelivered within 48 h of treatment initiation.
Sekundarni opazovani dogodki: Sekundarna merila učinkovitosti so vključevala delež žensk, ki niso rodile v 48 urah po začetku zdravljenja.
- if you are pregnant with more than one baby and/or are given medicines that can delay the birth of your baby, such as medicines used for high blood pressure.
- Če ste noseči z več kot enim otrokom in/ali jemljete zdravila, ki lahko odložijo porod vašega otroka, kot so zdravila, ki se uporabljajo za zdravljenje povišanega krvnega tlaka.
An intravenous microdrip chamber can provide a convenient range of infusion rates within the recommended dose levels for Tractocile.
Intravenska mikrokapalna komora lahko zagotavlja ustrezen razpon hitrosti infundiranja v priporočenih odmernih mejah za infundiranje zdravila Tractocile.
Colourless glass vials, clear borosilicated (type I) sealed with grey siliconised bromo-butyl rubber stopper, type I, and flip-off cap of polypropylene and aluminium.
Viala iz brezbarvnega, prozornega borosilikatnega stekla (tipa I), zaprta s sivim, silikoniziranim brombutilnim gumijastim zamaškom (tipa I) in »flip-off« zaporko iz polipropilena in aluminija.
Therefore, atosiban should be used with caution in case of multiple pregnancy and/or concomitant administration of other medicinal products with tocolytic activity (see section 4.8).
Zato je treba atosiban v primeru večplodne nosečnosti in/ali sočasne uporabe drugih zdravil s tokolitičnim delovanjem uporabljati previdno (glejte poglavje 4.8).
As the safety and efficacy of atosiban in women with a gestational age of less than 24 completed weeks has not been established in controlled randomised studies, the treatment of this patient group with atosiban is not recommended (see section 4.3).
Ker pri ženskah z gestacijsko starostjo manj kot 24 dopolnjenih tednov varnost in učinkovitost atosibana nista bili dokazani z nadzorovanimi randomiziranimi študijami, pri tej skupini bolnic uporaba atosibana ni priporočljiva (glejte poglavje 4.3).
Intravenous therapy using the initial bolus injection should be started as soon as possible after diagnosis of pre-term labour.
Intravensko zdravljenje z začetno bolusno injekcijo je treba začeti čimprej po diagnozi prezgodnjega poroda.
No studies were performed that covered fertility and early embryonic development (see section 5.3).
Študije, ki bi ocenile vpliv na plodnost in zgodnji razvoj zarodkov, niso bile izvedene (glejte poglavje 5.3).
Atosiban was also shown to bind to the vasopressin receptor, thus inhibiting the effect of vasopressin.
Dokazano je tudi, da se veže na receptor za vazopresin in tako zavre učinek vazopresina.
24 ml/hour (300 µg/min)
24 ml/uro (300 µg/min)
Fetal and maternal outcome did apparently not differ between the atosiban and the -agonist group, but the clinical studies were not powered enough to rule out a possible difference.
Izid za plod in mater se v skupini z atosibanom po vsem sodeč ni razlikoval od izida v skupini z -agonistom, toda moč kliničnih raziskav ni bila tolikšna, da bi izključila možno razliko.
Children and adolescents Tractocile has not been studied in pregnant women less than 18 years old.
Otroci in mladostniki Zdravilo Tractocile ni bilo preskušeno pri nosečnicah, starih manj kot 18 let.
- if you or your unborn baby have any other conditions where it would be dangerous to continue with your pregnancy.
- Če imate vi ali plod katerokoli drugo bolezensko stanje, zaradi katerega je nadaljevanje nosečnosti tvegano.
Preparation of the initial intravenous injection:
Priprava začetne intravenske injekcije:
Treatment failures caused by insufficient efficacy were significantly (p=0.0003) more frequent in atosiban (n=48, 14.2%) than in the -agonist-treated women (n=20, 5.8%).
Neuspešno zdravljenje zaradi nezadostne učinkovitosti je bilo značilno pogostejše (p = 0,0003) pri ženskah, ki so dobivale atosiban (n = 48, 14,2 %), kot pri ženskah, ki so dobivale agonist (n = 20, 5,8 %).
Eleven out of the 15 deaths in the atosiban group occurred in pregnancies with a gestational age of 20 to 24 weeks, although in this subgroup patient distribution was unequal (19 women on atosiban, 4 on placebo).
Enajst od 15 smrtnih primerov v skupini z atosibanom je bilo pri nosečnostih z gestacijsko starostjo od 20 do 24 tednov, čeprav je bila porazdelitev bolnic v tej podskupini neenakomerna (19 prejemnic atosibana, 4 prejemnice placeba).
Severe pre-eclampsia is when you have very high blood pressure, fluid retention and/or protein in your urine.
Za hudo preeklampsijo (nosečnostna toksemija) so značilni zelo visok krvni tlak, zastajanje tekočin in/ali prisotnost beljakovin v urinu.
In a placebo-controlled study, fetal/infant deaths were 5/295 (1.7%) in the placebo group and 15/288 (5.2%) in the atosiban group, of which two occurred at five and eight months of age.
V študiji, kontrolirani s placebom, je bilo v skupini s placebom 5 smrtnih primerov pri plodu/dojenčku (5/295; 1,7 %), v skupini z atosibanom pa 15 (15/288; 5,2 %), od tega dva v starosti pet in osem mesecev.
Reproduction toxicity studies, with dosing from implantation up to late stage pregnancy, showed no effects on mothers and fetuses.
Študije vplivov na sposobnost razmnoževanja z uporabo zdravila od nidacije do pozne nosečnosti niso pokazale nobenih učinkov na matere in zarodke.
When atosiban is used in patients in whom premature rupture of membranes cannot be excluded, the benefits of delaying delivery should be balanced against the potential risk of chorioamnionitis.
Če se atosiban uporablja pri bolnicah, pri katerih ni mogoče izključiti prezgodnjega razpoka plodnega mehurja, je treba koristi odloženega poroda pretehtati v primerjavi z možnim tveganjem za horioamnionitis.
- if your unborn baby is small for the time of your pregnancy.
- Če je plod premajhen za pretečeni čas nosečnosti.
After three hours the infusion rate is reduced to 8 ml/hour.
Po 3 urah je treba hitrost infundiranja zmanjšati na 8 ml/uro.
Phase III clinical trials (CAP-001 studies) include data from 742 women who were diagnosed with pre-term labour at 23-33 weeks of gestation and were randomised to receive either atosiban (according to this labelling) or -agonist (dose-titrated).
Klinična preskušanja III. faze (študije CAP-001) vključujejo podatke o 742 ženskah, pri katerih je bil diagnosticiran prezgodnji porod v obdobju od 22. do 33. tedna gestacije in so bile naključno razporejene tako, da so prejemale atosiban (odmerjanje v skladu s tem dokumentom) ali -agonist (titracija odmerka).
No systemic toxic effects were observed during the two-week intravenous toxicity studies (in rats and dogs) at doses which are approximately 10 times higher than the human therapeutic dose, and during the threemonths toxicity studies in rats and dogs (up to 20 mg/kg/day s.c.).
Pri dvotedenskih študijah toksičnosti (pri podganah in psih) z intravenskimi odmerki, ki so bili približno 10-krat večji od terapevtskega odmerka pri človeku, in pri trimesečnih študijah toksičnosti pri podganah in psih (do 20 mg/kg/dan s.c.) niso ugotovili sistemskih toksičnih učinkov.
Metabolite M1 is excreted in milk (see section 4.6).
Presnovek M1 se izloča z materinim mlekom (glejte poglavje 4.6).
The exposure of the rat fetus was approximately four times that received by the human fetus during intravenous infusions in women.
Izpostavljenost podganjih plodov je bila približno 4-krat večja od izpostavljenosti človeškega ploda med intravensko infuzijo pri materi.
4]-oxytocin) to atosiban concentrations in plasma were 1.4 and 2.8 at the second hour and at the end of the infusion respectively.
4]-oksitocin) in atosibana v plazmi je bilo po dveh urah 1,4 in na koncu infundiranja 2,8.
- allergic reactions
- Alergijske reakcije.
Small amounts of atosiban have been shown to pass from plasma into the breast milk of breast-feeding women.
Atosiban v majhnih količinah prehaja iz plazme v materino mleko.
Do not use this medicine after the expiry date which is stated on the label after EXP.
Tega zdravila ne smete uporabljati po datumu izteka roka uporabnosti, ki je naveden na nalepki poleg oznake EXP. Datum izteka roka uporabnosti se nanaša na zadnji dan navedenega meseca.
Following completion of the infusion, plasma concentration rapidly declined with an initial (tα) and terminal (tβ) half-life of 0.21 ± 0.01 and 1.7 ± 0.3 hours, respectively.
Po koncu infundiranja je koncentracija v plazmi hitro upadla z začetnim razpolovnim časom (tα) 0,21 ± 0,01 ure in s končnim razpolovnim časom (tβ) 1,7 ± 0,3 ure.
The observed adverse reactions were generally of a mild severity.
Opaženi neželeni učinki so bili običajno blagi.
What you need to know before you are given Tractocile
Kaj morate vedeti, preden boste prejeli zdravilo Tractocile
Treatment with Tractocile can be repeated up to three more times.
Zdravljenje z zdravilom Tractocile se lahko ponovi še največ trikrat.
In rats and guinea pigs, atosiban was shown to bind to oxytocin receptors, to decrease the frequency of contractions and the tone of the uterine musculature, resulting in a suppression of uterine contractions.
Pri podganah in budrah je dokazano, da se atosiban veže na receptorje za oksitocin, zmanjša pogostnost kontrakcij in tonus materničnega mišičja in tako zavre kontrakcije maternice.
Of the 361 women who received atosiban treatment in the phase III studies, 73 received at least one retreatment, 8 received at least 2 re-treatments and 2 received 3 re-treatments (see section 4.4).
Od 361 žensk, zdravljenih z atosibanom v študijah III. faze, je bilo zdravljenje ponovljeno vsaj enkrat pri 73 ženskah, vsaj dvakrat pri 8 ženskah, vsaj trikrat pa pri 2 ženskah (glejte poglavje 4.4).
Renal impairment is not likely to warrant a dose adjustment, since only a small extent of atosiban is excreted in the urine.
V primeru okvare ledvic odmerka verjetno ni treba prilagajati, saj se atosiban le v majhnem obsegu izloča z urinom.
There are no known side effects on the unborn or new-born baby.
Pri plodu ali novorojenčku ni znanih neželenih učinkov.
8 ml/hour (100 µg/min)
8 ml/uro (100 µg/min)
The following table shows the full posology of the bolus injection followed by the infusion:
V spodnji tabeli je prikazano celotno odmerjanje zdravila, ki se začne z injekcijo v obliki bolusa in nato nadaljuje z infuzijo:
Prepare new 100 ml bags in the same way as described to allow the infusion to be continued.
Na enak način, kot je opisan zgoraj, pripravite novo 100 ml vrečko, da se bo infuzija lahko nadaljevala.
The total dose given during a full course of Tractocile therapy should preferably not exceed 330.75 mg of atosiban.
Skupni odmerek atosibana med celotnim ciklusom zdravljenja z zdravilom Tractocile naj ne bi presegel 330,75 mg.
You may experience shortness of breath or lung oedema (accumulation of fluid in the lungs), particularly if you are pregnant with more than one baby and/or are given medicines that can delay the birth of your baby, such as medicines used for high blood pressure.
Lahko se pojavi težko dihanje ali pljučni edem (nabiranje tekočine v pljučih), še posebej, če ste noseči z več kot enim otrokom in/ali dobivate druga zdravila, ki lahko odložijo porod vašega otroka, kot so zdravila, ki se uporabljajo za zdravljenje povišanega krvnega tlaka.
As an antagonist of oxytocin, atosiban may theoretically facilitate uterine relaxation and postpartum bleeding therefore blood loss after delivery should be monitored.
Atosiban bi kot antagonist oksitocina teoretično lahko povzročil atonijo maternice in poporodno krvavitev, zato je po porodu treba nadzirati izgubo krvi.
Animal studies have shown inhibition of lactation as expected from the inhibition of action of oxytocin.
Raziskave na živalih so pokazale zaviralni učinek na dojenje, kar je pričakovano glede na zaviranje delovanja oksitocina.
If you are pregnant and breast-feeding an earlier child, you should stop breast-feeding while you are given Tractocile.
Če ste noseči in dojite starejšega otroka, boste morali prenehati z dojenjem, dokler dobivate zdravilo Tractocile.
Multiple pregnancy and medicinal products with tocolytic activity like calcium channel blockers and betamimetics are known to be associated with increased risk of pulmonary oedema.
Znano je, da sta mnogoplodna nosečnost in uporaba zdravil s tokolitičnim delovanjem, kot so zaviralci kalcijevih kanalčkov in beta-mimetiki, povezani z večjim tveganjem za pljučni edem.
- Keep this leaflet.
- Kožni izpuščaj.
What Tractocile looks like and contents of the pack
Izgled zdravila Tractocile in vsebina pakiranja
The proportion of atosiban eliminated in faeces is not known.
Delež v blatu izločenega atosibana ni znan.
It is unlikely that atosiban is involved in cytochrome P450 mediated drug-drug interactions as in vitro investigations have shown that atosiban is not a substrate for the cytochrome P450 system, and does not inhibit the drug metabolising cytochrome P450 enzymes.
Verjetnost, da je atosiban vpleten v interakcije z drugimi zdravili, ki se presnavljajo z encimi citokrom P450 je majhna, saj in vitro raziskave kažejo, da atosiban ni substrat za encime citokrom P450 in ne zavira encimov citokrom P450, ki presnavljajo zdravila.
Treatment should last no longer than 48 hours in total.
Zdravljenje v celoti ne sme trajati dlje kot 48 ur.
In women in pre-term labour receiving atosiban by infusion (300 micrograms/min for 6 to 12 hours), steady state plasma concentrations were reached within one hour following the start of the infusion (mean 442 ± 73 ng/ml, range 298 to 533 ng/ml).
Pri ženskah s prezgodnjim porodom, ki so dobile infuzijo atosibana (300 mikrogramov/min od 6 do 12 ur), so bile plazemske koncentracije v stanju dinamičnega ravnovesja dosežene v eni uri po začetku infuzije (povprečno 442 ± 73 ng/ml, razpon od 298 do 533 ng/ml).
There is only limited clinical experience in the use of atosiban in multiple pregnancies or the gestational age group between 24 and 27 weeks, because of the small number of patients treated.
Klinične izkušnje z uporabo atosibana pri mnogoplodnih nosečnostih ali v gestacijski starosti od 24. do 27. tedna so zaradi majhnega števila zdravljenih bolnic omejene.
- if your placenta is detaching from the wall of your womb.
- Če se je posteljica odluščila od stene maternice.
If during pregnancy the woman is already breast-feeding an earlier child, then breast-feeding should be discontinued during treatment with Tractocile, since the release of oxytocin during breast-feeding may augment uterine contractility, and may counteract the effect of tocolytic therapy.
Če nosečnica še doji prejšnjega otroka, mora med zdravljenjem z zdravilom Tractocile prenehati dojiti, saj lahko izločanje oksitocina med dojenjem okrepi maternične kontrakcije in nasprotuje učinkom tokolitičnega zdravljenja.
No clinically relevant interaction was found between atosiban and bethamethasone or labetalol.
Klinično pomembnih interakcij med atosibanom in betametazonom ali labetalolom niso opazili.
Following an infusion of 300 micrograms/min in healthy pregnant women at term, the fetal/maternal atosiban concentration ratio was 0.12.
Po infuziji 300 mikrogramov/min zdravim nosečnicam ob roku je bilo razmerje med koncentracijo atosibana pri plodu in materi 0,12.
Mean (SD) birth weight was 2491 (813) grams in the atosiban group and 2461 (831) grams in the -agonist group (p=0.58).
Povprečna (SD) porodna masa je bila v skupini z atosibanom 2.491 (813) gramov in v skupini z -agonistom 2.461 (831) gramov (p = 0,58).
Two metabolites were identified in the plasma and urine from human subjects.
V plazmi in urinu preiskovank so ugotovili dva presnovka.