Idatha entsha yokunciphisa uxinzelelo lwe-Fentanyl-Induced Respiratory kubasebenzisi be-Opioid engapheliyo

I-Indivior PLC ibhengeza ukupapashwa kwedatha yemodeli evavanya ukusebenzisana okukhuphisanayo phakathi kwe-buprenorphine, unyango lwe-opioid use disorder (OUD), kunye ne-fentanyl, i-opioid yokwenziwa enamandla, ukuqonda ngcono indlela i-buprenorphine enokunciphisa ngayo ukudakumba kwe-fentanyl-induced breathing. Uphononongo olunesihloko esithi "Imodeli yokunciphisa i-buprenorphine ye-fentanyl-induced breath depression" ifumaneka kwi-intanethi kwaye iya kuvela kwimiba yokuprinta ezayo ye-JCI Insight, iphephancwadi eliphononongwa ngontanga. Uphononongo luxhaswe ngu-Indivior.

Olu pho nonongo lwe-pharmacokinetic / pharmacodynamic lujolise ekuboniseni ukusebenzisana kwe-buprenorphine kunye ne-fentanyl kwinqanaba le-mu-opioid receptor (MOR) kwi-ventilation encinci phantsi kwamanqanaba aphezulu e-carbon dioxide kumavolontiya e-opioid-naïve kunye nabasebenzisi be-opioid engapheliyo. Idatha esetyenzisiweyo ukwenza imodeli yayisuka kuphononongo lwe-pharmacology yeklinikhi esanda kupapashwa kwi-PLOS ENYE. Injongo ephambili yomzekelo yayikukubonakalisa imiphumo yokunyuka kwemithamo ye-fentanyl ye-intravenous (0.25-0.70 mg / 70 kg uluhlu kubasebenzisi be-opioid engapheliyo) ekudakaleni kokuphefumula xa kuthelekiswa nokufakela nge-intravenous nokuba yi-placebo okanye i-buprenorphine ejolise kwi-plasma concentrations ngaphakathi kwe-0.2- 5 ng/mL uluhlu.

Amayeza e-Buprenorphine okuphazamiseka kokusetyenziswa kwe-opioid abonakaliswe ukunciphisa ukusetyenziswa kwe-opioid engekho mthethweni kunye nokufa okuhlobene ne-opioid. Olu hlalutyo luchaza enye indlela apho i-buprenorphine inokunciphisa ukufa kwe-opioid overdose. Idatha yemodeli ibonisa ukuba i-buprenorphine plasma concentrations ye-2 ng / mL kunye nephezulu inokuba nefuthe lokukhusela ngokuchasene ne-fentanyl-induced breath depression kubasebenzisi be-opioid engapheliyo, kunye nokunciphisa amathuba okuba ne-apnea emva kokuvezwa kwidosi ephezulu ye-fentanyl. Imodeli ibonisa ukuba xa ukuhlala kwe-MOR nge-buprenorphine kuphezulu ngokwaneleyo, i-fentanyl ayikwazi ukwenza i-MOR isebenze kwaye ngenxa yoko ayiyi kubangela ukudakumba okongeziweyo kokuphefumla ngaphezulu kweziphumo zokuphefumla ezithambileyo ze-buprenorphine kuloo bantu.

"Ezi datha zemodeli zibonisa ukuba i-buprenorphine plasma concentrations ye-2 ng / mL kunye nephezulu ibonakala inempembelelo yokukhusela kwi-fentanyl-induced breathing depression," kusho uChristian Heidbreder, PhD, iGosa eliyiNtloko lezeNzululwazi, i-Indivior. "Nangona uphononongo lomthombo luqhutywe kwindawo elawulwayo kunye nenani elincinci labasebenzisi be-opioid engapheliyo, ukukwazi kwe-buprenorphine ukunciphisa umngcipheko weziganeko ezinzulu zokuphefumla ezibangelwa yi-fentanyl zibonakalisiwe kwaye ziqinisekisa uphando olongezelelweyo kwimeko yelizwe lokwenyani. ”