FrancophonIA/ELRC3.0 huggingface dataset:
English: Longer-term repeat administration at cumulative exposures sufficiently exceeding the maximum intended human exposure produced toxicological effects in other organs, including the gastrointestinal tract and liver, and at the site of intravenous administration.
Croatian: Dugotrajna ponovljena primjena pri kumulativnim izloženostima koje su dovoljno prekoračivale najvišu planiranu izloženost u ljudi, izazvala je toksikološke učinke na druge organe, uključujući gastrointestinalni trakt i jetru, kao i na mjestu intravenske primjene.
English: Common C-reactive protein increased Uncommon Blood calcium decreased Observed in patients taking concomitant glucocorticosteroids.
Croatian: Pretrage često povišeni C-reaktivni protein manje često sniženi kalcij u krvi # Opaženo u bolesnika koji istodobno uzimaju glukokortikosteroide.
English: All patients received adequate supplementation with vitamin D and calcium in the post-menopausal osteoporosis trial, the prevention of clinical fractures after hip fracture trial, and the Paget's disease trials (see also section 4.2).
Croatian: Svi su bolesnici primili odgovarajuće nadomjestke vitamina D i kalcija u ispitivanju osteoporoze u postmenopauzi, prevenciji kliničkih prijeloma nakon ispitivanja prijeloma kuka te ispitivanjima Pagetove bolesti (vidjeti također dio 4.2).
English: When initiating treatment with zoledronic acid in patients with multiple myeloma or metastatic bone lesions from solid tumours, serum creatinine and creatinine clearance (CLcr) should be determined.
Croatian: Kad se počinje liječenje zoledronatnom kiselinom u bolesnika s multiplim mijelomom ili metastatskim koštanim lezijama solidnih tumora, potrebno je odrediti vrijednosti kreatinina u serumu i klirens kreatinina (CLcr).
English: The reduced doses for patients with renal impairment are expected to achieve the same AUC as that seen in patients with creatinine clearance of 75 ml/min.
Croatian: Očekuje se da će snižene doze u bolesnika s oštećenjem bubrega postići isti AUC kakav se opaža u bolesnika s klirensom kreatinina od 75 ml/min.
English: To assess the effects of 4 mg zoledronic acid versus pamidronate 90 mg, the results of two pivotal multicentre studies in patients with TIH were combined in a pre-planned analysis.
Croatian: Da bi se procijenili učinci 4 mg zoledronatne kiseline naspram 90 mg pamidronata, u unaprijed planiranoj analizi kombinirali su se rezultati dva ključna multicentrična ispitivanja u bolesnika s hiperkalcijemijom izazvanom tumorom.
English: Measurement of serum calcium before infusion of zoledronic acid is recommended for patients with Paget´s disease.
Croatian: Preporuča se mjerenje serumskog kalcija prije infuzije zoledronatne kiseline u bolesnika s Pagetovom bolesti.
English: − if you have or have had pain, swelling or numbness of the jaw, a feeling of heaviness in the jaw or loosening of a tooth.
Croatian: - ako imate ili ste imali bol, oticanje ili utrnulost čeljusti, težinu u čeljusti ili klimanje zuba.
English: Therefore, interactions resulting from displacement of highly protein-bound medicinal products are unlikely.
Croatian: Zbog toga, interakcije nastale istiskivanjem lijekova, koji su u velikoj mjeri vezani na proteine, nisu vjerojatne.
English: In the intravenous infusion studies, renal tolerability of zoledronic acid was established in rats when given 0.6 mg/kg as 15-minute infusions at 3-day intervals, six times in total (for a cumulative dose that corresponded to AUC levels about 6 times the human therapeutic exposure) while five 15-minute infusions of 0.25 mg/kg administered at 2-3-week intervals (a cumulative dose that corresponded to 7 times the human therapeutic exposure) were well tolerated in dogs.
Croatian: U ispitivanjima s intravenskom infuzijom, bubrežna podnošljivost zoledronatne kiseline utvrđena je u štakora kada su dobivali 0,6 mg/kg u obliku 15-minutne infuzije u intervalima od 3 dana, ukupno šest puta (čime se dobila kumulativna doza koja je odgovarala AUC razinama koje su bile otprilike 6 puta veće od terapijske izloženosti za ljude), dok su psi dobro podnosili pet 15-minutnih infuzija u dozi od 0,25 mg/kg primijenjenih u intervalima od 2-3 tjedna (kumulativna doza je odgovarala 7 puta većoj terapijskoj izloženosti za ljude).
English: Zoledronic acid is not highly bound to plasma proteins (approximately 43-55% bound) and binding is concentration independent.
Croatian: Zoledronatna kiselina se ne veže u velikoj mjeri na proteine plazme (veže se oko 43-55%), a vezanje ne ovisi o koncentraciji.
English: Your doctor, nurse or pharmacist knows how to store Zoledronic Acid Hospira properly (see section
Croatian: Vaš liječnik, medicinska sestra ili ljekarnik znaju kako ispravno čuvati Zoledronatnu kiselinu Hospira (vidjeti dio 6).
English: Other products containing zoledronic acid as active substance are available for osteoporosis indications and treatment of Paget´s disease of the bone.
Croatian: Dostupni su drugi lijekovi koji sadrže zoledronatnu kiselinu kao djelatnu tvar indiciranu kod osteoporoze i za liječenje Pagetove bolesti kostiju.
English: Median time to relapse (re-increase of albumin-corrected serum calcium 2.9 mmol/l) was 30 to 40 days for patients treated with zoledronic acid versus 17 days for those treated with pamidronate 90 mg (p-values: 0.001 for 4 mg and 0.007 for 8 mg zoledronic acid).
Croatian: Medijan vremena do relapsa (ponovnog povišenja kalcija u serumu korigiranog za albumin ≥ 2,9 mmol/l) iznosio je 30 do 40 dana u bolesnika liječenih zoledronatnom kiselinom naspram 17 dana u onih liječenih pamidronatom u dozi od 90 mg (pvrijednosti: 0,001 za 4 mg i 0,007 za 8 mg zoledronatne kiseline).
English: Five of the 6 patients had SAP within the normal range at month 6 (Late Observation Carried Forward, LOCF).
Croatian: Pet od 6 bolesnika imalo je razinu alkalne fosfataze u serumu unutar normalnih granica nakon 6 mjeseci (kasni period praćenja).
English: Adverse events occurring with frequencies < 5% were medically assessed and it was shown that these cases are consistent with the well established safety profile of zoledronic acid (see section 4.8)
Croatian: Štetni događaji koji nastaju s učestalošću < 5% bili su medicinski procijenjeni i pokazalo se da su ti slučajevi u skladu s dobro utvrđenim sigurnosnim profilom zoledronatne kiseline (vidjeti dio 4.8).
English: In clinical trials in osteoporosis, approximately 0.2% of patients had notable declines of serum calcium levels (less than 1.87 mmol/l) following zoledronic acid administration.
Croatian: Otprilike 0,2% bolesnika u kliničkom ispitivanju osteoporoze imalo je značajan pad razine kalcija u serumu (manje od 1,87 mmol/1) nakon primjene zoledronatne kiseline.
English: In patients with renal impairment, the systemic exposure to concomitant medicinal products that are primarily excreted via the kidney may increase.
Croatian: U bolesnika s oštećenjem bubrega, sistemska izloženost lijekovima koji se prvenstveno izlučuju putem bubrega, može se povećati.
English: Hypocalcaemia is an important identified risk with zoledronic acid in the approved indications.
Croatian: Hipokalcemija je važan identificirani rizik u primjeni zoledronatne kiseline u odobrenim indikacijama.
English: No pharmacokinetic data for zoledronic acid are available in patients with hypercalcaemia or in patients with hepatic insufficiency.
Croatian: Nema dostupnih farmakokinetičkih podataka za zoledronatnu kiselinu u bolesnika s hiperkalcijemijom ili bolesnika s teškom insuficijencijom jetre.
English: Patients with TIH and evidence of deterioration in renal function should be appropriately evaluated with consideration given as to whether the potential benefit of treatment with zoledronic acid outweighs the possible risk.
Croatian: Bolesnike s hiperkalcemijom izazvanom tumorom i dokazanim pogoršanjem funkcije bubrega treba procijeniti na odgovarajući način i pritom razmotriti jesu li moguće koristi od liječenja zoledronatnom kiselinom veće od mogućih rizika.
English: For the treatment of Paget's disease, zoledronic acid should be prescribed only by physicians with experience in the treatment of Paget's disease of the bone.
Croatian: Za liječenje Pagetove bolesti, zoledronatnu kiselinu treba propisati liječnik iskusan u liječenju Pagetove bolesti kostiju.
English: - If you are being treated to reduce the amount of calcium in your blood, you will normally only be given one infusion of Zoledronic Acid Hospira.
Croatian: - Ako se liječite radi snižavanja količine kalcija u krvi, obično ćete dobiti samo jednu infuziju
English: Intravenously administered zoledronic acid is eliminated by a triphasic process: rapid biphasic disappearance from the systemic circulation, with half-lives of t½α 0.24 and t½β 1.87 hours, followed by a long elimination phase with a terminal elimination half-life of t½γ 146 hours.
Croatian: Intravenski primijenjena zoledronatna kiselina eliminira se trofaznim procesom: brzi dvofazni nestanak iz sistemske cirkulacije, uz poluvijek t½α od 0,24 i t½β od 1,87 sati, nakon čega slijedi dugačka faza eliminacije s terminalnim poluvijekom eliminacije t½γ od 146 sati.
English: Severe and occasionally incapacitating bone, joint and/or muscle pain have been infrequently reported in patients taking bisphosphonates, including zoledronic acid (see section 4.8).
Croatian: Jaka i povremeno nepodnošljiva bol u kostima, zglobovima i/ili mišićima rijetko je prijavljena u bolesnika koji su uzimali bisfosfonate, uključujući zoledronatnu kiselinu (vidjeti dio 4.8).
English: Blood and lymphatic system disorders Common:
Croatian: Poremećaji krvi i limfnog sustava često:
English: Not known (frequency cannot be estimated from the available data) Severe allergic reactions including dizziness and difficulty breathing, swelling mainly of the face and throat, decreased blood pressure, dehydration secondary to post-dose symptoms such as fever, vomiting and diarrhoea.
Croatian: Nepoznato (učestalost se ne može procijeniti iz dostupnih podataka) Teške alergijske reakcije uključujući omaglicu i otežano disanje, oticanje uglavnom lica i vrata, pad krvnog tlaka, dehidraciju nakon pojave simptoma kao što su vrućica, povraćanje i proljev.
English: Zoledronic acid is not metabolised and is excreted unchanged via the kidney.
Croatian: Zoledronatna kiselina se ne metabolizira i izlučuje se nepromijenjena putem bubrega.
English: • Zoledronic acid should be used with caution when concomitantly used with other medicinal products that could impact renal function (see section 4.5).
Croatian: • zoledronatnu kiselinu treba primijeniti s oprezom kada se istodobno daje s drugim lijekovima koji mogu oštetiti funkciju bubrega (vidjeti dio 4.5)
English: Patients who were classified as responders at the end of the 6 month core study were eligible to enter an extended follow-up period.
Croatian: Bolesnici koji su na kraju šestomjesečnog osnovnog kliničkog ispitivanja bili klasificirani kao osobe koje pokazuju terapijski odgovor bili su prikladni za uključenje u produljeni period praćenja.
English: Your doctor, pharmacist or nurse knows how to store Zoledronic Acid Hospira properly.
Croatian: Vaš liječnik, ljekarnik ili medicinska sestra znaju kako ispravno čuvati Zoledronatnu kiselinu Hospira.
English: The following precautions should be taken into account to minimise the risk of renal adverse reactions:
Croatian: Potrebno je poduzeti sljedeće mjere opreza radi smanjenja rizika bubrežnih nuspojava:
English: In the single-dose dog infusion studies, 1.0 mg/kg (6 fold the recommended human therapeutic exposure based on AUC) administered over 15 minutes was well tolerated with no renal effects.
Croatian: U ispitivanjima pojedinačne doze infuzijom u pasa, doza od 1,0 mg/kg (šesterostruko viša od preporučene terapijske izloženosti za ljude bazirano na AUC-u) primijenjena u trajanju od 15 minuta bila je dobro podnesena, bez učinaka na bubrege.
English: No interaction studies with other medicinal products have been performed with zoledronic acid.
Croatian: Specifična ispitivanja interakcija između lijekova nisu provedena sa zoledronatnom kiselinom.
English: A subset had recurrence of symptoms when rechallenged with zoledronic acid or another bisphosphonate.
Croatian: U dijela tih bolesnika simptomi su se vratili nakon ponovnog liječenja zoledronatnom kiselinom ili drugim bisfosfonatom.
English: Interstitial lung disease (inflammation of the tissue around the air sacks of the lungs)
Croatian: - bolest intersticija pluća (upalna bolest tkiva oko zračnih mjehurića u plućima)
English: In patients with mild to moderate renal impairment, reduced doses should be prepared as instructed below.
Croatian: U bolesnika s blagim do umjerenim oštećenjem bubrega potrebno je pripremiti smanjene doze prema niže navedenim uputama.
English: What Zoledronic Acid Hospira looks like and contents of the pack Zoledronic Acid Hospira is a clear and colourless solution.
Croatian: Kako Zoledronatna kiselina Hospira izgleda i sadržaj pakiranja Zoledronatna kiselina Hospira je bistra i bezbojna otopina.
English: There was a transient increase in serum creatinine observed within 10 days in 1.8% of zoledronic acid-treated patients versus 0.8% of placebo-treated patients.
Croatian: Opaženo je prolazno povećanje kreatinina u serumu unutar 10 dana u 1,8% bolesnika liječenih zoledronatnom kiselinom naspram 0,8% bolesnika koji su primali placebo.
English: In some instances, the hypocalcaemia may be life-threatening (see section 4.8).
Croatian: U nekim slučajevima hipokalcemija je bila životnougrožavajuća (vidjeti dio 4.8).
English: Small observed increases in AUC(0-24hr), by about 30% to 40% in mild to moderate renal impairment, compared to a patient with normal renal function, and lack of accumulation of medicinal product with multiple doses irrespective of renal function, suggest that dose adjustments of zoledronic acid in mild (Clcr = 50-80 ml/min) and moderate renal impairment down to a creatinine clearance of 35 ml/min are not necessary.
Croatian: Mala opažena povećanja AUC (0-24hr) vrijednosti za oko 30% do 40% u slučaju blagog do umjerenog oštećenja bubrega naspram bolesnika s normalnom funkcijom bubrega te pomanjkanje akumulacije lijeka pri višekratnim dozama bez obzira na bubrežnu funkciju, navode na zaključak da nije potrebno prilagođavati dozu zoledronatne kiseline u slučaju blagog (Clcr = 50-80 ml/min) i umjerenog oštećenja bubrega s klirensom kreatinina do 35 ml/min.
English: Administration of 0.001 mg/kg/day subcutaneously in rats and 0.005 mg/kg intravenously once every 2-3 days in dogs for up to 52 weeks was also well tolerated.
Croatian: Doza od 0,001 mg/kg na dan primijenjena supkutano u štakora i doza od 0,005 mg/kg primijenjena intravenski u pasa jednom svaka 2-3 dana do najviše 52 tjedna također su se dobro podnosile.
English: Zoledronic acid shows no appreciable binding to plasma proteins and does not inhibit human P450 enzymes in vitro (see section 5.2), but no formal clinical interaction studies have been performed.
Croatian: Zoledronatna kiselina se ne veže u nekoj zamjetnoj mjeri za proteine plazme i ne inhibira ljudske enzime P450 in vitro (vidjeti dio 5.2), ali nisu provedena formalna klinička ispitivanja interakcija.
English: Single and multiple 5 and 15-minute infusions of 2, 4, 8 and 16 mg zoledronic acid in 64 patients yielded the following pharmacokinetic data, which were found to be dose independent.
Croatian: Jednokratnim i višekratnim 5-minutnim i 15-minutnim infuzijama 2, 4, 8 i 16 mg zoledronatne kiseline u 64 bolesnika dobiveni su sljedeći farmakokinetički podaci za koje se utvrdilo da ne ovise o dozi.
English: Dystocia was observed at the lowest dose (0.01 mg/kg body weight) tested in rats.
Croatian: Distocija je bila opažena pri najnižoj dozi (0,01 mg/kg tjelesne težine) ispitanoj u štakora.
English: The infusion time must not be less than 15 minutes.
Croatian: Vrijeme inuzije ne smije biti kraće od 15 minuta.
English: Hypocalcaemia has been reported in patients treated with zoledronic acid.
Croatian: Hipokalcemija je prijavljena u bolesnika koji su liječeni zoledronatnom kiselinom.
English: - Prevention of skeletal related events (pathological fractures, spinal compression, radiation or surgery to bone, or tumour-induced hypercalcaemia) in adult patients with advanced malignancies involving bone.
Croatian: - Prevencija koštanih događaja (patološki prijelomi, spinalna kompresija, zračenje ili kirurški zahvat na kosti ili hiperkalcijemija izazvana tumorom) u odraslih bolesnika s uznapredovalom zloćudnom bolešću koja je zahvatila kost.
English: Zoledronic acid 4 mg significantly reduced the proportion of patients experiencing at least one skeletal related event (SRE), delayed the median time to first SRE by > 5 months, and reduced the annual incidence of events per patient - skeletal morbidity rate.
Croatian: Zoledronatna kiselina u dozi od 4 mg značajno je smanjila udio bolesnika s najmanje jednim koštanim događajem, produljila medijan vremena do prvog koštanog događaja za > 5 mjeseci i smanjila godišnju incidenciju događaja po bolesniku - stopu koštanog pobola.
English: Very rare:
Croatian: uveitis vrlo rijetko:
English: The overall percentage of patients who experienced adverse reactions were 44.7%, 16.7% and 10.2% after the first, second and third infusion, respectively.
Croatian: Ukupan postotak bolesnika koji su imali nuspojave nakon prve, druge i treće infuzije iznosio je 44,7%, 16,7% i 10,2%.
English: During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.
Croatian: Bolesnicima treba savjetovati da tijekom liječenja bisfosfonatima prijave svaku bol u bedru, kuku ili preponama, a svakog bolesnika s takvim simptomima treba pregledati na nepotpuni prijelom bedrene kosti.
English: Zoledronic acid is not highly bound to plasma proteins (approximately 43-55% bound) and interactions resulting from displacement of highly protein-bound medicinal products are therefore unlikely.
Croatian: Zoledronatna kiselina se ne veže u nekoj zamjetnoj mjeri za proteine plazme (približno 43-55% vezanja), stoga nisu vjerojatne interakcije zbog preraspodjele lijeka koji se veže za proteine u znatnoj mjeri.
English: Increases in serum creatinine also occur in some patients with chronic administration of zoledronic acid at recommended doses for prevention of skeletal related events, although less frequently.
Croatian: U nekih bolesnika dolazi do povišenja kreatinina u serumu i kod kronične primjene zoledronatne kiseline u dozama koje se preporučuju za prevenciju koštanih događaja, iako manje učestalo.
English: Your doctor may recommend a dental examination before you start treatment with Zoledronic Acid Hospira - if you are having dental treatment or are due to undergo dental surgery, tell your dentist that you are being treated with Zoledronic Acid Hospira and inform your doctor about your dental treatment.
Croatian: Vaš liječnik može preporučiti pregled kod zubara prije nego počnete liječenje Zoledronatnom kiselinom Hospira - ako se liječite kod zubara ili trebate ići na zubarski kirurški zahvat, obavijestite svog zubara da se liječite Zoledronatnom kiselinom Hospira i obavijestite svog liječnika o Vašem liječenju kod zubara.
English: In an in vitro study, zoledronic acid showed low affinity for the cellular components of human blood, with a mean blood to plasma concentration ratio of 0.59 in a concentration range of 30 ng/ml to 5000 ng/ml.
Croatian: U in vitro ispitivanju, zoledronatna kiselina je pokazala niski afinitet za ljudske krvne stanice, uz srednju vrijednost omjera koncentracije krvi prema plazmi od 0,59 za raspon koncentracije od 30 ng/ml do 5000 ng/ml.
English: The European Medicines Agency has waived the obligation to submit the results of studies with the reference medicinal product containing zoledronic acid in all subsets of the paediatric population in Paget's disease of the bone (see section 4.2 for information on paediatric use).
Croatian: Europska agencija za lijekove ukinula je obvezu podnošenja rezultata ispitivanja referentnog lijeka koji sadrži zoledronatnu kiselinu u svim podskupinama pedijatrijske populacije u Pagetovoj bolesti kosti (vidjeti dio 4.2 za informacije o pedijatrijskoj primjeni).
English: An extension study was conducted in order to examine the long-term general and renal safety of once yearly or twice yearly zoledronic acid over the 12-month extension treatment period in children who had completed one year of treatment with either zoledronic acid or pamidronate in the core study.
Croatian: Produžetak ispitivanja proveo se da bi se ispitala dugotrajna opća sigurnost zoledronatne kiseline i njezina sigurnost za bubrege kod primjene jednom ili dvaput godišnje tijekom 12-mjesečnog produžetka razdoblja liječenja u djece koja su dovršila godinu dana liječenja zoledronatnom kiselinom ili pamidronatom u glavnom ispitivanju.
English: Following initiation of therapy, serum creatinine should be measured prior to each dose of Zoledronic Acid Hospira and treatment should be withheld if renal function has deteriorated.
Croatian: Nakon početka terapije kreatinin u serumu treba mjeriti prije svake doze zoledronatne kiseline, a liječenje treba obustaviti ako se funkcija bubrega pogorša.
English: If you have pre-existing hypocalcaemia, it must be corrected before initiating the first dose of Zoledronic Acid Hospira.
Croatian: Ako već imate hipokalcemiju, ona se mora korigirati prije uvođenja prve doze Zoledronatne kiseline Hospira.
English: In the intravenous bolus studies, the doses that were well-tolerated decreased with increasing study duration: 0.2 and 0.02 mg/kg daily was well tolerated for 4 weeks in rats and dogs, respectively but only 0.01 mg/kg and 0.005 mg/kg in rats and dogs, respectively, when given for 52 weeks.
Croatian: U ispitivanjima s intravenskom bolus injekcijom, doze koje su se dobro podnosile su se smanjivale s povećanjem trajanja ispitivanja: dozu od 0,2 i 0,02 mg/kg dnevno dobro su podnosili štakori, odnosno psi tijekom 4 tjedna, no nakon 52 tjedna primjene štakori su podnosili dozu od samo 0,01 mg/kg, a psi od samo 0,005 mg/kg.
English: Zoledronic acid 4 mg was also studied in a double-blind, randomised, placebo-controlled trial in 228 patients with documented bone metastases from breast cancer to evaluate the effect of 4 mg zoledronic acid on the skeletal related event (SRE) rate ratio, calculated as the total number of SRE events (excluding hypercalcaemia and adjusted for prior fracture), divided by the total risk period.
Croatian: Zoledronatna kiselina od 4 mg također se ispitivala u dvostruko slijepom, randomiziranom, placebom kontroliranom ispitivanju u 228 bolesnika s potvrđenim koštanim metastazama raka dojke da bi se procijenio učinak 4 mg zoledronatne kiseline na omjer stope koštanih događaja izračunatog kao ukupni broj koštanih događaja (bez hiperkalcemije i prilagođen s obzirom na prethodne prijelome) podijeljen s ukupnim rizičnim razdobljem.
English: Zoledronic acid was well tolerated when administered subcutaneously to rats and intravenously to dogs at doses up to 0.02 mg/kg daily for 4 weeks.
Croatian: Zoledronatna kiselina dobro se podnosila kad se primjenjivala supkutano štakorima i intravenski psima u dozama do 0,02 mg/kg dnevno tijekom 4 tjedna.
English: This medicinal product must not be allowed to come into contact with any calcium-containing solutions.
Croatian: Ovaj lijek ne smije doći u kontakt s otopinama koje sadrže kalcij.
English: Not known**
Croatian: Prijelomi*
English: Marketing Authorisation Holder Pfizer Europe MA EEIG Boulevard de la Plaine 17 1050 Bruxelles
Croatian: Pfizer Europe MA EEIG Boulevard de la Plaine 17 1050 Bruxelles
English: The total body clearance is 5.04 ± 2.5 l/h, independent of dose, and unaffected by gender, age, race, and body weight.
Croatian: Ukupni klirens iz tijela je 5,04±2,5 l/h, neovisan o dozi i na njega ne utječu spol, dob, rasa i tjelesna težina.
English: Only limited pharmacokinetic data are available in patients with severe renal insufficiency (creatinine clearance < 30 ml/min).
Croatian: Za bolesnike s teškom insuficijencijom bubrega dostupni su samo ograničeni farmakokinetički podaci (klirens kreatinina < 30 ml/min).