natgillin/translations-raw huggingface dataset:
Elvitegravir, emtricitabin og tenofoviralafenamid viste synergistisk antiviral aktivitet i cellekultur.
Elvitegravir, emtricitabine, and tenofovir alafenamide demonstrated synergistic antiviral activity in cell culture.
Baseret på disse begrænsede data lignede sikkerhedsprofilen for Genvoya hos patienter co-inficeret med hiv/HBV den for patienter med hiv 1-monoinfektion.
Based on these limited data, the safety profile of Genvoya in patients with HIV/HBV co-infection was similar to that in patients with HIV-1 monoinfection.
• antidepressiva, anvendes til at behandle depression: lægemidler, der indeholder trazodon eller escitalopram
• antidepressants, used to treat depression: medicines containing trazodone or escitalopram
Gennemsnitsalderen var 58 år (interval 24-82) med 63 patienter (26 %), som var ≥ 65 år.
The mean age was 58 years (range 24-82), with 63 patients (26%) who were ≥ 65 years of age.
Hæmning af CYP3A-medieret metabolisme af cobicistat øger den systemiske eksponering over for CYP3A-substrater, såsom elvitegravir, hvor biotilgængeligheden er begrænset og halveringstiden er forkortet af den CYP3A-afhængige metabolisme.
Inhibition of CYP3A-mediated metabolism by cobicistat enhances the systemic exposure of CYP3A substrates, such as elvitegravir, where bioavailability is limited and half-life is shortened by CYP3A-dependent metabolism.
13 % af emtricitabindosen blev genfundet i urinen som tre metabolitter.
Thirteen percent of the emtricitabine dose was recovered in urine as three metabolites.
På baggrund af information fra litteraturen og i produktinformationen for lægemidler der indeholder integrasehæmmere, kunne det dog konkluderes, at følgende psykiske lidelser: depression, selvmordstanker og selvmordsadfærd (især hos patienter med psykisk sygdom i anamnesen) er klasseeffekt af integrasehæmmere, og disse er anført i produktresuméet for andre lægemidler indeholdende integrasehæmmere i monoterapi og i fastdosiskombination.
However, based on the information retrieved in literature and in the product information of integrase inhibitors containing medicinal products, it could be concluded that the following psychiatric disorders: depression, suicidal ideation and suicidal behaviour (particularly in patients with pre-existing history of psychiatric illness) are class-effect of integrase inhibitors and these are listed in the SmPC of other medicinal products containing integrase inhibitors in monotherapy and in fixed-dose combination (FDC).
Da der er en lavere eksponering for tenofovir hos rotter og mus efter administration af tenofoviralafenamid sammenlignet med tenofovirdisoproxil, blev der kun udført karcinogenicitetsstudier og et peri-postnatalt studie hos rotter med tenofovirdisoproxil.
Because there is a lower tenofovir exposure in rats and mice after the administration of tenofovir alafenamide compared to tenofovir disoproxil, carcinogenicity studies and a rat peri-postnatal study were conducted only with tenofovir disoproxil.
EVG = elvitegravir; COBI = cobicistat; FTC = emtricitabin; TAF = tenofoviralafenamidfumarat; TFV = tenofovir N/A = ikke relevant
EVG = elvitegravir; COBI = cobicistat; FTC = emtricitabine; TAF = tenofovir alafenamide fumarate; TFV = tenofovir N/A = not applicable
• adefovirdipivoxil
• adefovir dipivoxil
• ergot-derivater: dihydroergotamin, ergometrin, ergotamin
• ergot derivatives: dihydroergotamine, ergometrine, ergotamine
Genvoya udviste statistisk superioritet ved at opnå hiv 1-rna < 50 kopier/ml, sammenlignet med E/C/F/TDF ved uge 144.
Genvoya demonstrated statistical superiority in achieving HIV-1 RNA < 50 copies/mL when compared to E/C/F/TDF at Week 144.
Efter administration af tenofoviralafenamid viste plasma [14C]-radioaktivitet en tidsafhængig profil med tenofoviralafenamid som det hyppigste stof i de første par timer og urinsyre i den resterende periode.
Following administration of tenofovir alafenamide, plasma [14C]-radioactivity showed a time-dependent profile with tenofovir alafenamide as the most abundant species in the initial few hours and uric acid in the remaining period.
Ud af de 10 patienter, som ikke var supprimerede ved baseline (HBV DNA ≥ 29 IE/ml), blev 7 supprimerede, 2 forblev detekterbare, og 1 havde manglende data.
Of the 10 patients who were not HBV suppressed at baseline (HBV DNA ≥ 29 IU/mL), 7 became suppressed, 2 remained detectable, and 1 had missing data.
Cobicistat har ingen målelig antiviral aktivitet mod hiv 1, og antagoniserer ikke de antivirale virkninger af elvitegravir, emtricitabin og tenofovir.
Cobicistat has no detectable antiviral activity against HIV-1 and does not antagonise the antiviral effects of elvitegravir, emtricitabine, or tenofovir.
Cobicistat er også en svag CYP2D6-hæmmer, og den metaboliseres i mindre grad af CYP2D6.
Cobicistat is also a weak CYP2D6 inhibitor and is metabolised, to a minor extent, by CYP2D6.
Grønne, kapselformede, filmovertrukne tabletter, der måler 19 mm x 8,5 mm, præget med ”GSI” på den ene side af tabletten og med ”510” på den anden side af tabletten.
Green, capsule-shaped, film-coated tablet of dimensions 19 mm x 8.5 mm, debossed with “GSI” on one side of the tablet and “510” on the other side of the tablet.
Baseret på lægemiddelinteraktionsstudier udført med Genvoya eller Genvoya-komponenterne, er der ikke blevet observeret og der forventes heller ikke nogen klinisk signifikante lægemiddelinteraktioner mellem Genvoya-komponenterne og de følgende lægemidler: entecavir, famciclovir, ribavirin, famotidin og omeprazol.
Based on drug-drug interaction studies conducted with Genvoya or the components of Genvoya, no clinically significant drug-drug interactions have been either observed or are expected between the components of Genvoya and the following medicinal products: entecavir, famciclovir, ribavirin, famotidine, and omeprazole.
Efter oral administration sammen med mad hos hiv 1-inficerede patienter blev maksimale plasmakoncentrationer observeret ca. 4 timer efter dosering for elvitegravir, 3 timer efter dosering for cobicistat, 3 timer efter dosering for emtricitabin og 1 time efter dosering for tenofoviralafenamid.
Following oral administration with food in HIV-1 infected patients, peak plasma concentrations were observed approximately 4 hours post-dose for elvitegravir, 3 hours post-dose for cobicistat, 3 hours post-dose for emtricitabine, and 1 hour post-dose for tenofovir alafenamide.
Ved screening fik 42 % af patienterne FTC/tenofovirdisoproxil plus atazanavir (boosted enten ved cobicistat eller ritonavir), 32 % af patienterne fik E/C/F/TDF, og 26 % af patienterne fik EFV/FTC/tenofovirdisoproxil.
At screening, 42% of patients were receiving FTC/tenofovir disoproxil plus atazanavir (boosted by either cobicistat or ritonavir), 32% of patients were receiving E/C/F/TDF, and 26% of patients were receiving EFV/FTC/tenofovir disoproxil.
Emtricitabin-eksponeringer blev ikke påvirket af et let måltid eller et måltid med højt fedtindhold.
Emtricitabine exposures were unaffected by a light or high-fat meal.
De indberettede resultater fra et prospektivt studie (IMPAACT P1026s) viste, at behandling med regimer indeholdende cobicistat og elvitegravir under graditet medfører lavere eksponering for elvitegravir og cobicistat (Tabel 7).
The results reported from a prospective study (IMPAACT P1026s) showed that treatment with cobicistat and elvitegravir-containing regimens during pregnancy results in lower elvitegravir and cobicistat exposures (Table 7).
Elvitegravir/cobicistat/emtricitabin/tenofoviralafenamid Dette lægemiddel er underlagt supplerende overvågning.
Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide This medicine is subject to additional monitoring.
De beskrevne interaktioner er baseret på studier udført med Genvoya eller Genvoya-komponenterne (elvitegravir, cobicistat, emtricitabin og tenofoviralafenamid) som individuelle stoffer og/eller i kombination, eller de er mulige lægemiddelinteraktioner, der kan forekomme med Genvoya.
The interactions described are based on studies conducted with Genvoya, or the components of Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide), as individual agents and/or in combination, or are potential drug-drug interactions that may occur with Genvoya.
Dosisjustering af clarithromycin er ikke nødvendig.
No dose adjustment of clarithromycin is required.
Lægemidler, der er meget afhængige af CYP3A-metabolismen og som har en høj first pass-metabolisme, er mest udsatte for meget øget eksponering, når de administreres sammen med cobicistat (se ”Samtidig brug kontraindiceret” og pkt.
Medicinal products that are highly dependent on CYP3A metabolism and have high first pass metabolism are the most susceptible to large increases in exposure when co-administered with cobicistat (see “Concomitant use contraindicated” and section 4.3).
Et farmakokinetikstudie af cobicistat-boosted elvitegravir blev udført hos non-hiv 1-inficerede patienter med moderat nedsat leverfunktion (Child-Pugh klasse B).
A study of the pharmacokinetics of cobicistat-boosted elvitegravir was performed in non-HIV-1 infected patients with moderate hepatic impairment (Child-Pugh Class B).
Tabel 4: Virologiske resultater af studie GS-US-292-0109 ved uge 48a og 96b Uge 48
Table 4: Virologic outcomes of Study GS-US-292-0109 at Weeks 48a and 96b
Både elvitegravir og cobicistat metaboliseres og udskilles primært i leveren.
Both elvitegravir and cobicistat are primarily metabolised and eliminated by the liver.
Tenofoviralafenamid er et substrat for OATP in vitro.
Tenofovir alafenamide is a substrate of OATP in vitro.
I kliniske studier af mennesker resulterede en 10 mg oral dosis af tenofoviralafenamid i Genvoya i tenofovirdiphosphatkoncentrationer > 4 gange højere i PBMC'er og > 90 % lavere koncentrationer af tenofovir i plasma sammenlignet med en 245 mg oral dosis af tenofovirdisoproxil (som fumarat) i E/C/F/TDF.
In human clinical studies, a 10 mg oral dose of tenofovir alafenamide in Genvoya resulted in tenofovir diphosphate concentrations > 4-fold higher in PBMCs and > 90% lower concentrations of tenofovir in plasma as compared to a 245 mg oral dose of tenofovir disoproxil (as fumarate) in E/C/F/TDF.
• Hvis De er allergisk over for elvitegravir, cobicistat, emtricitabin, tenofoviralafenamid eller et af de øvrige indholdsstoffer i Genvoya (angivet i punkt 6 i denne indlægsseddel).
• If you are allergic to elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide or any of the other ingredients of this medicine (listed in section 6 of this leaflet).
Virkningen af svært nedsat leverfunktion (Child-Pugh klasse C) på elvitegravirs og cobicistats farmakokinetik er ikke undersøgt.
The effect of severe hepatic impairment (Child-Pugh Class C) on the pharmacokinetics of elvitegravir or cobicistat has not been studied.
Elvitegravir var negativ i en in vitro bakteriel mutagenicitetstest (Ames-test) og negativ i en in vivo mikronukleusanalyse med rotter ved doser op til 2.000 mg/kg.
Elvitegravir was negative in an in vitro bacterial mutagenicity test (Ames test) and negative in an in vivo rat micronucleus assay at doses up to 2,000 mg/kg.
Den mediane stigning fra baseline for disse parametre var større i Genvoya-gruppen sammenlignet med E/C/F/TDFgruppen ved uge 144 (p < 0,001 for forskellen mellem behandlingsgrupperne for fastende total kolesterol, direkte LDL- og HDL-kolesterol samt triglycerider).
The median increase from baseline for those parameters was greater in the Genvoya group compared with the E/C/F/TDF group at Week 144 (p < 0.001 for the difference between treatment groups for fasting total cholesterol, direct LDL- and HDL-cholesterol, and triglycerides).
• syreneutraliserende midler, anvendes til at behandle halsbrand (se også punkt 3, Sådan skal De tage Genvoya).
• antacids, used to treat heartburn or acid reflux (see also section 3, How to take Genvoya).
ANTIKOAGULANTIA Dabigatran
ANTICOAGULANTS Dabigatran
Hvis patienten glemmer at tage en dosis Genvoya i mere end 18 timer, skal patienten ikke tage den manglende dosis, men blot fortsætte med den normale doseringsplan.
If a patient misses a dose of Genvoya by more than 18 hours, the patient should not take the missed dose and simply resume the usual dosing schedule.
Ved starten af behandlingen med Genvoya havde 72 patienter været hiv-supprimerede (hiv-1 RNA < 50 kopier/ml) i mindst 6 måneder med eller uden supprimering af HBV DNA, og de havde kompenseret leverfunktion.
At the start of treatment with Genvoya, the 72 patients had been HIV suppressed (HIV-1 RNA < 50 copies/mL) for at least 6 months with or without suppression of HBV DNA and had compensated liver function.
Tag ikke syreneutraliserende midler eller multivitaminer på samme tidspunkt som Genvoya.
Do not take antacids or multivitamins at the same time as Genvoya.
Det anbefales at overvåge den internationale normaliserede ratio (INR) ved samtidig administration af Genvoya.
It is recommended that the international normalised ratio (INR) be monitored upon co-administration of Genvoya.
Cobicistat er 97-98 % bundet til humane plasmaproteiner og forholdet mellem gennemsnitlig lægemiddelkoncentration i plasma og blodet var 2.
Cobicistat is 97-98% bound to human plasma proteins and the mean plasma to blood drug concentration ratio was 2.
Ved samtidig administration af Genvoya bør den maksimale daglige dosis af ketoconazol ikke overskride 200 mg daglig.
When administering with Genvoya, the maximum daily dose of ketoconazole should not exceed 200 mg per day.
Cobicistat hæmmer MATE1 reversibelt, og koncentrationer af metformin kan øges ved samtidig administration af Genvoya.
Cobicistat reversibly inhibits MATE1, and concentrations of metformin may be increased when co-administered with Genvoya.
Elvitegravir metaboliseres primært af CYP3A, og lægemidler, der inducerer eller hæmmer CYP3A kan påvirke eksponeringen of elvitegravir.
Elvitegravir is primarily metabolised by CYP3A, and medicinal products that induce or inhibit CYP3A may affect the exposure of elvitegravir.
Hjælpestoffer, som behandleren skal være opmærksom på Hver tablet indeholder 61 mg lactose (som monohydrat).
Each tablet contains 61 mg lactose (as monohydrate).
Tabel 7: Ændringer i farmakokinetiske elvitegravir- og cobisistat-parametre fra studiet IMPAACT P1026s hos kvinder, der fik regimer indeholdende cobicistat og elvitegravir i andet og tredje trimester af graviditeten, sammenlignet med parrede postpartumdata
Table 7: Changes in pharmacokinetic parameters from the IMPAACT P1026s study for elvitegravir and cobicistat in women receiving cobicistat and elvitegravir-containing regimens during the second and third trimesters of pregnancy compared to paired postpartum data
Genvoya bør ikke administreres samtidig med andre antiretrovirale lægemidler.
Genvoya should not be co-administered with other antiretroviral medicinal products.
Cobicistat er en selektiv, mekanismebaseret hæmmer af cytokrom P450 (CYP)-enzymer fra CYP3A-undergruppen.
Cobicistat is a selective, mechanism-based inhibitor of cytochrome P450 (CYP) enzymes of the CYP3A subfamily.
selvmordstanker og selvmordsforsøg (hos patienter med depression eller psykisk sygdom i anamnesen), depression2
suicidal ideation and suicide attempt (in patients with a pre-existing history of depression or psychiatric illness), depression2
Hold ikke op med at tage Genvoya Hold ikke op med at tage Genvoya uden at tale med Deres læge.
Do not stop taking Genvoya without talking to your doctor.
Der er begrænsede kliniske data vedrørende brugen af Genvoya hos patienter med samtidig infektion med hiv/HBV, som er behandlingsnaive.
There are limited clinical data on the use of Genvoya in HIV/HBV co-infected patients who are treatment-naïve.
Der blev observeret lignende mønstre for psykiske lidelser i komparative studier af elvitegravir/cobicistat/emtricitabin/tenofoviralafenamid (E/C/F/TAF) versus elvitegravir/cobicistat/emtricitabin/tenofovirdisoproxilfumarat (E/C/F/TDF), som angiver disse hændelser i produktinformationen (studie GS-US-292-0104 eller GS-US-292-0111).
Similar patterns of psychiatric disorders were observed in comparative studies of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) versus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), which lists these events in its product information (studies GS-US-292-0104 or GS-US-292-0111).
• sedativa og hypnotika, anvendes til at behandle angst: - buspiron, clorazepat, diazepam, estazolam, flurazepam, zolpidem og lorazepam
• sedatives and hypnotics, used to treat anxiety: buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem and lorazepam
betamethason, budesonid, fluticason, mometason, prednison og triamcinolon.
betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone.
Unge og børn i alderen 6 år og ældre, som vejer mindst 25 kg: en tablet om dagen sammen med mad
Adolescents and children 6 years of age and older, who weigh at least 25 kg: one tablet each day with food
Sofosbuvir metabolit GS-331007:
Sofosbuvir metabolite GS-331007:
Hos behandlingsnaive patienter blev der observeret en gennemsnitlig ændring fra baseline på 0,04 ± 0,12 mg/dl (3,5 ± 10,6 μmol/l) efter 144 ugers behandling.
In treatment-naïve patients, a mean change from baseline of 0.04 ± 0.12 mg/dL (3.5 ± 10.6 µmol/L) was observed after 144 weeks of treatment.
Genvoyas sikkerhed og virkning hos patienter med signifikant underliggende leversygdom er ikke klarlagt.
The safety and efficacy of Genvoya in patients with significant underlying liver disorders have not been established.
Antiviral synergi blev opretholdt for elvitegravir, emtricitabin og tenofoviralafenamid, når det blev testet, mens cobicistat var til stede.
Antiviral synergy was maintained for elvitegravir, emtricitabine, and tenofovir alafenamide when tested in the presence of cobicistat.
• antibiotika, der anvendes til at behandle bakterieinfektioner, herunder tuberkulose, og indeholder: rifabutin, clarithromycin og telithromycin
• antibiotics, used to treat bacterial infections including tuberculosis, containing: rifabutin, clarithromycin and telithromycin
In vitro-resistens over for cobicistat kan ikke påvises da cobicistat har ingen antivirale aktivitet.
No in vitro resistance can be demonstrated with cobicistat due to its lack of antiviral activity.
Den mediane terminale halveringstid i plasma for cobicistat efter administration af E/C/F/TDF er ca. 3,5 timer, og de forbundne cobicistat-eksponeringer giver en Ctrough for elvitegravir, der er ca. 10 gange over IC95 justeret for proteinbinding for vildtype hiv 1-virus.
The median terminal plasma half-life of cobicistat following administration of E/C/F/TDF is approximately 3.5 hours and the associated cobicistat exposures provide elvitegravir Ctrough approximately 10-fold above the protein-binding adjusted IC95 for wild-type HIV-1 virus.
Cobicistat og tenofoviralafenamid er ikke hæmmere af humant UGT1A1 in vitro.
Cobicistat and tenofovir alafenamide are not inhibitors of human UGT1A1 in vitro.
Ved samtidig administration af cobicistat i Genvoya opnås der imidlertid næsten maksimal hæmning af P-gp af cobicistat, hvilket fører til en øget tilgængelighed af tenofoviralafenamid og resulterende eksponeringer, der svarer til tenofoviralafenamid 25 mg administreret alene.
However, upon co-administration with cobicistat in Genvoya, near maximal inhibition of P-gp by cobicistat is achieved leading to increased availability of tenofovir alafenamide with resulting exposures comparable to tenofovir alafenamide 25 mg administered alone.
Hiv 1 med de raltegravir-udvalgte substitutioner T66A/K, Q148H/K og N155H viste krydsresistens over for elvitegravir.
HIV-1 with the raltegravir-selected substitutions T66A/K, Q148H/K, and N155H showed cross-resistance to elvitegravir.
En minimal infiltration af histiocytter var til stede i øjet på hunde ved eksponeringer over for hhv. tenofoviralafenamid og tenofovir, der var ca. 4 og 17 gange større, end hvad der forventes efter administration af Genvoya.
A minimal infiltration of histiocytes was present in the eye in dogs at tenofovir alafenamide and tenofovir exposures of approximately 4 and 17 times greater, respectively, than those expected after administration of Genvoya.
Plasmakoncentrationerne af drospirenon forventes at øges efter samtidig administration med Genvoya, og klinisk monitorering anbefales på grund af risikoen for hyperkaliæmi (se pkt.
Plasma concentrations of drospirenone are expected to be increased following co-administration with Genvoya and clinical monitoring is recommended due to the potential for hyperkalaemia (see section 4.5).
2 Denne bivirkning blev ikke observeret i kliniske fase 3-studier for Genvoya, men blev identificeret i kliniske studier for elvitegravir ved anvendelse sammen med andre antiretrovirale midler.
2 This adverse reaction was not observed in the Phase 3 clinical studies for Genvoya but identified from clinical studies for elvitegravir when used with other antiretrovirals.
I et separat fase 1-studie af emtricitabin alene var den gennemsnitlige systemiske emtricitabin-eksponering højere hos patienter med svært nedsat nyrefunktion (estimeret CrCl < 30 ml/min) (33,7 µg•t/ml) end hos personer med normal nyrefunktion (11,8 µg•t/ml).
In a separate Phase 1 study of emtricitabine alone, mean systemic emtricitabine exposure was higher in patients with severe renal impairment (estimated CrCl < 30 mL/min) (33.7 µg•h/mL) than in subjects with normal renal function (11.8 µg•h/mL).
1 Denne bivirkning blev ikke observeret i kliniske fase 3-studier for Genvoya, men blev identificeret i kliniske studier eller fra erfaring efter markedsføring for emtricitabin ved anvendelse sammen med andre antiretrovirale midler.
1 This adverse reaction was not observed in the Phase 3 clinical studies for Genvoya but identified from clinical studies or post-marketing experience for emtricitabine when used with other antiretrovirals.
Brug af anden medicin sammen med Genvoya Fortæl altid lægen eller apotekspersonalet, hvis De tager anden medicin eller har gjort det for nylig.
Other medicines and Genvoya Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Interaktion er ikke undersøgt med nogen af Genvoyas komponenter.
Interaction not studied with any of the components of Genvoya.
Elvitegravir indebærer en risiko for at inducere CYP2C9 og/eller inducerbare uridindiphosphatglucuronosyltransferase (UGT)-enzymer, og derved reducere plasmakoncentrationen af substrater for disse enzymer.
Elvitegravir may have the potential to induce CYP2C9 and/or inducible uridine diphosphate glucuronosyltransferase (UGT) enzymes; as such it may decrease the plasma concentration of substrates of these enzymes.
Hvis patienten kaster op inden for 1 time efter at have taget Genvoya, skal der tages en ny tablet.
If the patient vomits within 1 hour of taking Genvoya another tablet should be taken.
Genvoya frarådes hos patienter med en estimeret CrCl ≥ 15 ml/min og < 30 ml/min eller < 15 ml/min, som ikke er i kronisk hæmodialyse, da Genvoyas sikkerhed hos disse populationer ikke er blevet klarlagt.
Genvoya should be avoided in patients with estimated CrCl ≥ 15 mL/min and < 30 mL/min, or < 15 mL/min who are not on chronic haemodialysis, as the safety of Genvoya has not been established in these populations.
I forhold til fastende tilstand påvirkede administrationen af Genvoya sammen med et let måltid (~400 kcal, 20 % fedtindhold) eller et måltid med højt fedtindhold (~800 kcal, 50 % fedt) ikke den samlede eksponering for tenofoviralafenamid i en klinisk signifikant grad (ca. 15 % og 18 % højere AUC med hhv. et let måltid eller et måltid med højt fedtindhold kontra fastende).
Relative to fasting conditions, the administration of Genvoya with a light meal (~400 kcal, 20% fat) or high-fat meal (~800 kcal, 50% fat) did not affect overall exposures of tenofovir alafenamide to a clinically meaningful extent (approximately 15% and 18% higher AUC with a light or high-fat meal, respectively, versus fasted).