natgillin/translations-raw huggingface dataset:
Der er rapporteret tilfælde med kompromitteret respirationsfrekvens og dybde og med livstruende respirationsdepression, som gjorde intubation og ventilation nødvendig.
There are reports of compromise in the rate and depth of respiration and of life-threatening respiratory depression, necessitating intubation and ventilation.
Cheyne - Stokes respiration og apnø har været observeret.
Cheyne-Stokes respiration and apnoea have been observed.
Bradycardi og hypothermi kan følge med bevidstløshed, lige så vel som muskulær hypotoni med intakte senereflexer.
Bradycardia and hypothermia may accompany unconsciousness, as well as muscular hypotonia, but tendon reflexes remain intact.
Tømning af ventriklen bør overvejes ved mistanke om samtidig indtag af andre stoffer.
Gastric lavage may be considered if co-ingestants are suspected.
Da emesis kan opstå i tilfælde med bevidsthedssløring, skal nødvendig lejring (aflåst sideleje) og beskyttelse af luftvejene ved intubation sikres.
Because emesis may occur in the presence of impaired consciousness, appropriate posture (left lateral recumbent position) and protection of the airway by intubation may be warranted.
Selvom brækreflexen kan forsvinde hos dybt komatøse patienter, kan selv bevidstløse patienter modarbejde intubation, og hurtig sekvens induktion (uden brug af sedativa) bør overvejes.
Although gag reflex may be absent in deeply comatose patients, even unconscious patients may become combative to intubation, and rapid sequence induction (without the use of sedative) should be considered.
Der kan ikke forventes reversion af den CNS- depressive effekt af natriumoxybat ved administration af flumazenil.
No reversal of the central depressant effects of sodium oxybate can be expected from flumazenil administration.
Der er ikke tilstrækkelig evidens til at anbefale brug af naloxon til behandling af en overdosis med GHB.
There is insufficient evidence to recommend the use of naloxone in the treatment of overdose with GHB.
Brug af hæmodialyse eller andre metoder til ekstrakorporal lægemiddel elimination har ikke været undersøgt i forbindelse med natriumoxybat overdosis.
The use of haemodialysis and other forms of extracorporeal drug removal have not been studied in sodium oxybate overdose.
Men, på grund af den hurtige metabolisme af natriumoxybat kan disse tiltag ikke betale sig.
However, due to the rapid metabolism of sodium oxybate, these measures are not warranted.
Andre midler med virkning på centralnervesystemet, ATC- kode:
Other Nervous System Drugs, ATC code:
N07XX04 hydroxybutansyre.
N07XX04 hydroxybutyric acid
Natriumoxybat er et CNS- depressivt lægemiddel, som nedsætter udtalt søvnighed om dagen og katapleksi i dagtimerne hos patienter med narkolepsi og modificerer søvnmønsteret samt reducerer afbrudt nattesøvn.
Sodium oxybate is a central nervous system depressant which reduces excessive daytime sleepiness and cataplexy in patients with narcolepsy and modifies sleep architecture reducing fragmented nighttime sleep.
Den præcise mekanisme med hvilken natriumoxybat har effekt på narkolepsi er ukendt, men natriumoxybat tænkes at virke ved at promovere slow (delta) wave søvn og konsolidere søvnen om natten.
The precise mechanism by which sodium oxybate produces an effect is unknown, however sodium oxybate is thought to act by promoting slow (delta) wave sleep and consolidating night-time sleep.
Natriumoxybat administreret før nattesøvnen øger søvnstadie 3 og 4 og øger søvnlatens, mens det reducerer frekvensen af ’ sleep onset REM perioder ’ (SOREMPs).
Sodium oxybate administered before nocturnal sleep increases Stages 3 and 4 sleep and increases sleep latency, whilst reducing the frequency of sleep onset REM periods (SOREMPs).
Andre mekanismer, som stadig mangler at blive klarlagt kan også være involveret.
Other mechanisms, which have yet to be elucidated, may also be involved.
I den kliniske forsøgsdatabase fortsatte mere end 80% af patienterne med samtidig anvendelse af stimulerende midler.
In the clinical trial database, greater than 80% of patients maintained concomitant stimulant use.
Samtidig anvendelse af stimulerende midler var tilladt i alle forsøg (undtaget den aktive behandlingsfase i forsøg 2); antidepressiva blev seponeret før den aktive behandling i alle forsøg med undtagelse af forsøg 2.
The effectiveness of sodium oxybate for the treatment of narcolepsy symptoms was established in four multicentre, randomised, double-blind, placebo-controlled, parallel-group trials (Trial 1, 2, 3 and 4) in patients with narcolepsy with cataplexy except for trial 2 where cataplexy was not required for enrolment Concomitant stimulant use was permitted in all trials (except for the active-treatment phase of Trial 2); antidepressants were withdrawn prior to active treatment in all trials with the exception of Trial 2.
I hvert forsøg blev den daglige dosis fordelt på to lige store doser.
In each trial, the daily dose was divided into two equal doses.
Hver nat blev den første dosis taget ved sengetid og den anden dosis blev taget 2, 5 til 4 timer senere.
The first dose each night was taken at bedtime and the second dose was taken 2.5 to 4 hours later.
Tabel 1 narkolepsi
Table 1 Narcolepsy
Sammenfatning af kliniske forsøg ved anvendelse af natriumoxybat til behandling af
Summary of Clinical Trials Performed Using Sodium Oxybate for the Treatment of
Forsøg
Trial
Primær effekt N= Sekundær Varighed
Primary N= Secondary Efficacy Duration
effekt
Efficacy
behandling og dosering (g/ d)
treatment and Dose (g/ d)
EDS (ESS);
EDS (ESS); CGIc
MWT/ Sleep
MWT/ Sleep Architecture/ Cataplexy/ Naps/ FOSQ
Xyrem 4, 5- 9
Xyrem 4.5 - 9
Katapleksi/ Naps/ FOSQ Forsøg 2
Trial 2
Sleep Architecture / ESS/ CGIc/ Naps
Sleep Architecture/ ESS/ CGIc/ Naps
8 uger Xyrem 6- 9 Modafinil 200- 600 mg
Xyrem 6 – 9 Modafinil 200-600 mg
Forsøg 3 Forsøg 4
Trial 3
Katapleksi Katapleksi
Cataplexy
136 55
136
EDS (ESS) / CGIc/ Naps None
EDS (ESS)/ CGIc/ Naps
4 uger 4 uger
Xyrem 3 - 9
Xyrem 3- 9 Xyrem 3- 9
Cataplexy
EDS – Excessive daytime sleepiness (Udtalt søvnighed om dagen); ESS – Epworth Sleepiness Scale (Epsworths scala for søvnighed); MWT – Maintenance of Wakefulness Test (Test for opretholdelse af vågenhed); Naps (episoder med lur) – Number of inadvertent daytime naps( antal af uundgåelige episoder med lur om dagen); CGIc – Clinical Global Impression of Change (Klinisk global vurdering af ændring); FOSQ – Functional Outcomes of Sleep Questionnaire (Funktionelle resultater fra spørgeskema om søvn).
EDS – Excessive daytime sleepiness; ESS – Epworth Sleepiness Scale; MWT – Maintenance of Wakefulness Test; Naps – Number of inadvertent daytime naps; CGIc – Clinical Global Impression of Change; FOSQ – Functional Outcomes of Sleep Questionnaire
Forsøg 1 inkluderede 246 patienter med narkolepsi og omfattede en uges optitreringsperiode.
Trial 1 enrolled 246 patients with narcolepsy and incorporated a 1 week up-titration period.
Denne alvorlighed blev fastsat ved brug af Clinical Global Impressions of Change (CGI- c) - målingen af den ansvarlige læge for undersøgelsen.
The primary measures of efficacy were changes in excessive daytime sleepiness as measured by the Epworth Sleepiness Scale (ESS), and the change in the overall severity of the patient’ s narcolepsy symptoms as assessed by the investigator using the Clinical Global Impressions of Change (CGI-c) measure.
8 Tabel 2
8 Table 2
Sammenfatning af ESS i forsøg 1
Summary of ESS in Trial 1
Epworth Sleepiness Scale (ESS; range 0- 24)
Epworth Sleepiness Scale (ESS; range 0-24)
Doseringsgruppe [g/ d (n)]
Dose Group [g/ d (n)]
Median afvigelse fra baseline
Median Change from Baseline
Afvigelse fra baseline sammenlignet med placebo (p- værdi)
Change from Baseline Compared to Placebo (p-value)
Placebo (60) 4, 5 (68) 6 (63) 9 (55)
Placebo (60) 4.5 (68) 6 (63) 9 (55)
17, 3 17, 5 17, 9 17, 9
17.3 17.5 17.9 17.9
16, 7 15, 7 15, 3 13, 1
16.7 15.7 15.3 13.1
- 0, 5 - 1, 0 - 2, 0 - 2, 0
-0.5 -1.0 -2.0 -2.0
- 0, 119 0, 001 < 0, 001
- 0.119 0.001 < 0.001
Sammenfatning af CGI- c i forsøg 1
Summary of CGI-c in Trial 1
Doseringsgruppe [g/ d (n)]
Clinical Global Impressions of Change (CGI-c) Dose Group [g/ d (n)]
Responderende patienter * N (%)
Responders* N (%)
13 (21, 7) 32 (47, 1) 30 (47, 6) 30 (54, 4)
13 (21.7) 32 (47.1) 30 (47.6) 30 (54.4)
- 0, 002 < 0, 001 < 0, 001
- 0.002 < 0.001 < 0.001
* CGI- c data blev analyseret således, at responderende patienter blev defineret som de patienter der fik det rigtig meget bedre eller meget bedre.
* The CGI-c data were analysed by defining responders as those patients who were very much improved or much improved.
Forsøg 2 sammenlignede virkningen af oralt administreret natriumoxybat, modafinil og natriumoxybat + modafinil, med placebo til behandling af søvnighed i dagtimerne ved narkolepsi.
Trial 2 compared the effects of orally administered sodium oxybate, modafinil and sodium oxybate + modafinil, with placebo in the treatment of daytime sleepiness in narcolepsy.
Under den 8 ugers dobbeltblinde periode, tog patienterne enten modafinil som fast dosis eller tilsvarende placebo.
During the 8 week double-blind period, patients took modafinil at their established dose or placebo equivalent.
Natriumoxybatdosis og den ækvivalerende placebodosis var på 6 g/ dag de første 4 uger og blev øget til 9 g/ dag i de resterende 4 uger.
The sodium oxybate or placebo equivalent dose was 6g/ day for the first 4 weeks and was increased to 9g/ day for the remaining 4 weeks.
Den primære måling af effekt var udtalt søvnighed i dagtimerne som målt ved objektiv respons i MWT.
The primary measure of efficacy was excessive daytime sleepiness as measured by objective response in MWT.
Sammenfatning af MWT i forsøg 2 FORSØG 2
Summary of MWT in Trial 2
Doseringsgruppe
Dose Group
Den gennemsnitlige afvigelse fra baseline
Mean Change from
Endpoint sammenlignet med placebo
Endpoint
Natriumoxybat (55) Modafinil (63) Natriumoxybat + Modafinil (57)
Sodium Oxybate (55) Modafinil (63) Sodium Oxybate + Modafinil (57)
Forsøg 3 involverede 136 narkolepsipatienter med moderat til alvorlig katapleksi (median på 21 katapleksianfald per uge) ved baseline.
Trial 3 enrolled 136 narcoleptic patients with moderate to severe cataplexy (median of 21 cataplexy attacks per week) at baseline.
De primære målinger af effekt i dette forsøg, omfattede frekvensen af katapleksianfald.
The primary efficacy measure in this trial was the frequency of cataplexy attacks.
Sammenfatning af resultat i
Summary of Outcomes in Trial 3
Katapleksianfald
Number of Cataplexy Attacks Subjects
Forsøg
Trial 3
Afvigelse fra baseline sammenlignet med placebo
Change Baseline Compared Placebo value)
(p- værdi)
from to (p-
6, 0 g/ day 9, 0 g/ day
Median attacks/ week Placebo 3.0 g/ day 6.0 g/ day 9.0 g/ day
31 33
33 33 31 33
23, 0 23, 5
20.5 20.0 23.0 23.5
- 10 - 16
-4 -7 -10 -16
0, 0529 0, 0008
- 0.5235 0.0529 0.0008
Forsøg 4 involverede 55 narkolepsipatienter, som åbent havde taget natriumoxybat i 7 til 44 måneder.
Trial 4 enrolled 55 narcoleptic patients who had been taking open-label sodium oxybate for 7 to 44 months.
Patienterne randomiseredes til fortsat behandling med natriumoxybat i deres fastsatte dosis eller til placebo.
Patients were randomised to continued treatment with sodium oxybate at their stable dose or to placebo.
Forsøg 4 var designet specifikt for at vurdere den fortsatte effekt af natriumoxybat efter langtidsbrug.
Trial 4 was designed specifically to evaluate the continued efficacy of sodium oxybate after long-term use.
Den primære måling af effekt i dette forsøg omfattede hyppigheden af katapleksianfald.
The primary efficacy measure in this trial was the frequency of cataplexy attacks.
Sammenfatning af resultat i Forsøg 4
Summary of outcome in Trial 4
Antal patienter Baseline
Number of Baseline Subjects
Afvigelse fra baseline sammenlignet med placebo
Change Baseline Compared Placebo (p-value)
(p- værdi) Forsøg 4
Trial 4
Median anfald/ to uger
Median attacks/ two
I forsøg 4 var svaret numerisk tilsvarende for patienter behandlet med doser på 6 til 9 g/ dag, men ingen effekt observeredes hos patienter behandlet med lavere doser end 6 g/ dag.
In Trial 4, the response was numerically similar for patients treated with doses of 6 to 9 g/ day, but there was no effect seen in patients treated with doses less than 6 g/ day.
Natriumoxybat absorberes hurtigt men ufuldstændigt efter oral administration, absorptionen forsinkes og nedsættes ved indtag af måltider med højt fedtindhold.
Sodium oxybate is rapidly but incompletely absorbed after oral administration; absorption is delayed and decreased by a high fat meal.
Det udskilles hovedsageligt ved metabolisme med en halveringstid på 0, 5 – 1 time.
It is eliminated mainly by metabolism with a half-life of 0.5 to 1 hour.
Farmakokinetikken er non- lineær med øgning af arealet under plasma koncentrations kurven (AUC) versus tidskurven på 3. 8 gange når dosis fordobles fra 4, 5 g til 9 g.
Pharmacokinetics are nonlinear with the area under the plasma concentration curve (AUC) versus time curve increasing 3.8-fold as dose is doubled from 4.5g to 9g.
Farmakokinetikken ændres ikke med gentagne doser.
The pharmacokinetics are not altered with repeat dosing.
Natriumoxybat absorberes hurtigt efter oral administration med en absolut biotilgængelighed på omkring 25%.
Sodium oxybate is absorbed rapidly following oral administration with an absolute bioavailability of about 25%.
Gennemsnitlig maksimale plasmakoncentrationer (første og andet maksimum), efter administration af en 9 g daglig dosis fordelt på to lige store doser givet med 4 timers mellemrum, var henholdsvis 78 og 142 μg/ ml.
The average peak plasma concentrations (1st and 2nd peak) following administration of a 9 g daily dose divided into two equivalent doses given four hours apart were 78 and 142 μ g/ ml, respectively.
Den gennemsnitlige tid til peak plasma koncentrationer (Tmax) strakte sig fra 0, 5 til 2 timer i otte farmakokinetiske studier.
The average time to peak plasma concentration (Tmax) ranged from 0.5 to 2 hours in eight pharmacokinetic studies.
Efter oral administration øges plasmaniveauer af natriumoxybat mere end proportionalt med hver dosis øgning.
Following oral administration, the plasma levels of sodium oxybate increase more than proportionally with increasing dose.
Enkeltdoser over 4, 5 g har ikke været undersøgt.
Single doses greater than 4.5 g have not been studied.
Administration af natriumoxybat ummiddelbart efter et måltid med højt fedtindhold resulterede i forsinket absorption (gennemsnitlig Tmax steg fra 0, 75 timer til 2, 0 timer) og en reduktion i peak plasma niveau (Cmax) med gennemsnitlig 58% og systemisk tilgængelighed (AUC) med 37%.
Administration of sodium oxybate immediately after a high fat meal resulted in delayed absorption (average Tmax increased from 0.75 hr to 2.0 hr) and a reduction in peak plasma level (Cmax) by a mean of 58% and of systemic exposure (AUC) by 37%.
10 Distribution:
10 Distribution:
Natriumoxybat er et hydrofilt stof med et tilsyneladende fordelingsvolumen på gennemsnitlig 190- 384 ml/ kg.
Sodium oxybate is a hydrophilic compound with an apparent volume of distribution averaging 190-384 ml/ kg.
Ved natriumoxybat koncentrationer fra 3 til 300 μg/ ml, er mindre end 1% bundet til plasmaproteiner.
At sodium oxybate concentrations ranging from 3 to 300 μ g/ ml, less than 1% is bound to plasma proteins.
Dyrestudier tyder på at metabolisme er den mest betydningsfulde udskillelsesvej for natriumoxybat, ved produktion af kuldioxid og vand via Krebs cyklus og sekundært ved β- oxidation.
Animal studies indicate that metabolism is the major elimination pathway for sodium oxybate, producing carbon dioxide and water via the tricarboxylic acid (Krebs) cycle and secondarily by β -oxidation.
Den primære vej involverer et cytosol NADP+- forbundet enzym, GHB dehydrogenase, som katalyserer omdannelsen af natriumoxybat til succinylsemialdehyd, som derefter biotransformeres til succinylsyre af enzymet succinylsemialdehyddehydrogenase.
The primary pathway involves a cytosolic NADP+-linked enzyme, GHB dehydrogenase, that catalyses the conversion of sodium oxybate to succinic semialdehyde, which is then biotransformed to succinic acid by the enzyme succinic semialdehyde dehydrogenase.
Succinylsyre indgår i Krebs cyklus, hvor det metaboliseres til kuldioxid og vand.
Succinic acid enters the Krebs cycle where it is metabolised to carbon dioxide and water.
Et andet mitochondrielt oxidoreduktase enzym, en transhydrogenase, katalyserer også omdannelsen til succinylsemialdehyd i tilstedeværelse af α - ketoglutarat.
A second mitochondrial oxidoreductase enzyme, a transhydrogenase, also catalyses the conversion to succinic semialdehyde in the presence of α -ketoglutarate.
En alternativ biotransformations vej involverer β- oxidation via 3, 4- dihydroxybutyrat til Acetyl CoA, som derefter indgår i citronsyrecyklus resulterende i dannelsen af kuldioxid og vand.
An alternate pathway of biotransformation involves β -oxidation via 3,4-dihydroxybutyrate to Acetyl CoA, which also enters the citric acid cycle to result in the formation of carbon dioxide and water.
In vitro studier med poolede humane lever microsomer indikerer at natriumoxybat ikke signifikant hæmmer aktiviteten af de humane isoenzymer:
Studies in vitro with pooled human liver microsomes indicate that sodium oxybate does not significantly inhibit the activities of the human isoenzymes:
CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, eller CYP3A op til en koncentration på 3 mM (378 μg/ ml).
CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A up to the concentration of 3 mM (378 μ g/ ml).
Disse niveauer er væsentlig højere end dem der opnås med terapeutiske doser.
These levels are considerably higher than levels achieved with therapeutic doses.
I gennemsnit forekommer mindre end 5% uændret lægemiddel i human urin indenfor 6 til 8 timer efter dosering.
On average, less than 5% of unchanged drug appears in human urine within 6 to 8 hours after dosing.
Specielle patientkategorier
Special Populations:
Farmakokinetikken for natriumoxybat i patienter ældre end 65 år er ikke undersøgt.
The pharmacokinetics of sodium oxybate in patients greater than the age of 65 years have not been studied.
Fordi nyrerne ikke har en signifikant rolle i udskillelsen af natriumoxybat, er der ikke foretaget farmakokinetiske studier med patienter med nedsat nyrefunktion; ingen effekt på nyrefunktionen er forventelig.
Because the kidney does not have a significant role in the excretion of sodium oxybate, no pharmacokinetic study in patients with renal dysfunction has been conducted; no effect of renal function on sodium oxybate pharmacokinetics would be expected.
Lever sygdom:
Hepatic Disease:
Natriumoxybat undergår signifikant præsystemisk (hepatisk first- pass) metabolisme.
Sodium oxybate undergoes significant presystemic (hepatic first-pass) metabolism.
Efter en enkel oral dosis på 25 mg/ kg, fordobles AUC værdier hos cirrotiske patienter, med en tilsyneladende oral clearance reduktion fra 9, 1 hos raske voksne til 4, 5 og 4, 1 ml/ min/ kg henholdsvis i klasse A (uden ascites) og klasse C (med ascites).
After a single oral dose of 25 mg/ kg, AUC values were double in cirrhotic patients, with apparent oral clearance reduced from 9.1 in healthy adults to 4.5 and 4.1 ml/ min/ kg in Class A (without ascites) and Class C (with ascites) patients, respectively.
Eliminations - halveringstiden var signifikant længere i klasse C og klasse A patienter end i kontrolgruppen (mean t1/ 2 på 59 og 32 versus 22 minutter).
Elimination half-life was significantly longer in Class C and Class A patients than in control subjects (mean t1/ 2 of 59 and 32 versus 22 minutes).
4. 2).
It is prudent to reduce the starting dose of sodium oxybate by one-half in patients with liver dysfunction (see Section 4.2).
Gentagen administration af natriumoxybat til rotter (90 dage og 26 uger) og til hunde (52 uger) resulterede ikke i nogle signifikante fund i den kliniske kemi og mikro - og makro patologi.
Repeat administration of sodium oxybate to rats (90 days and 26 weeks) and dogs (52 weeks) did not result in any significant findings in clinical chemistry and micro- and macro pathology.
Behandlingsrelaterede kliniske tegn var hovedsagelig relateret til sedation, formindsket indtagelse af føde og sekundære forandringer i legemsvægt, vægtøgning og organvægt.
Treatment- related clinical signs were mainly related to sedation, reduced food consumption and secondary changes in body weight, body weight gain and organ weights.
Rotte og hunde eksponeringer ved NOEL var lavere (~50%) end dem på mennesker.
The rat and dog exposures at the NOEL were lower (~50%) than that in humans.
Natriumoxybat var ikke - mutagent og ikke- klastogent i in vitro og in vivo forsøg.
Sodium oxybate was non-mutagenic and non-clastogenic in in vitro and in vivo assays.
11 Gamma Butyrolacton (GBL), en pro- drug til GHB, som testedes ved eksponering svarende til den, som forventedes i mennesker (1, 21- 1, 64 gange), er klassifiseret ved NTP som ikke- karcinogen på rotter og usikker karcinogen på mus, på grund af en lille stigning i fæokromocytom, hvilken var vanskeligt at tyde på grund af høj dødelighed i højdosis gruppen.
11 Gamma Butyrolactone (GBL), a pro-drug of GHB tested at exposures similar to the expected in man (1.21-1.64 times) has been classified by NTP as non-carcinogenic in rats and equivocal carcinogen in mice, due to slight increase of pheochromocytomas which was difficult to interpret due to high mortality in the high dose group.
I et karcinogenicitets forsøg på rotter med oxybat identificeredes ingen substans- relaterede tumorer.
In a rat carcinogenicity study with oxybate no compound-related tumours were identified.
GHB havde ingen effekt på parring, almen fertilitet eller sperm parametre og forårsagede ikke embryo- føtal toksicitet hos rotter eksponerede for op til 1000 mg/ kg/ dag GHB (1, 64 gange den menneskelige eksponering udregnet i ikke- gravide dyr).
GHB had no effect on mating, general fertility or sperm parameters and did not produce embryo-foetal toxicity in rats exposed to up 1000 mg/ kg/ day GHB (1.64 times the human exposure calculated in nonpregnant animals).
Perinatal mortalitet steg og gennemsnitsvægten for unger blev nedsat i amningsperioden hos højdosis F1 dyr.
Perinatal mortality was increased and mean pup weight was decreased during the lactation period in high-dose F1 animals.
Sammenhæng mellem disse udviklingseffekter og maternal toksicitet kunne ikke dokumenteres.
The association of these developmental effects with maternal toxicity could not be established.
Lægemiddeldiskriminations forsøg viser at GHB forårsager en unik diskriminativ stimulus som i visse henseender ligner den som findes i alkohol, morfin og visse GABA- lignende lægemidler.
Drug discrimination studies show that GHB produces a unique discriminative stimulus that in some respects is similar to that of alcohol, morphine and certain GABA-mimetic drugs.
Selv - administrerings forsøg på rotter, mus og aber har vist modstridende resultater, mens tolerance for GHB ligesom krydstolerance mod alkohol tydeligt er demonstreret hos gnavere.
Self-administration studies in rats, mice and monkeys have produced conflicting results, whereas tolerance to GHB as well as cross-tolerance to alcohol have been clearly demonstrated in rodents.
Vand, renset, æblesyre til pH justering natriumhydroxid til pH justering
Purified water Malic acid for pH adjustment Sodium Hydroxide for pH adjustment
6. 3 Opbevaringstid
6.3 Shelf life 5 years
Efter første åbning:
After First opening:
40 dage.
40 days
Efter fortynding i målebægeret (se punkt 4. 2), skal opløsningen bruges inden for 24 timer.
After dilution in the dosing cups (see Section 4.2), the preparation should be used within 24 hours.
Gulligfarvet oval PET flaske med børnesikret lukke af HDPE/ propylen med en LDPE indsats tilpasset med en PVC anbrudssikret forsegling.
Amber oval PET bottle with a child resistant closure composed of HDPE/ polypropylene with a LDPE liner fitted with a PVC tamper evident seal.