Nō nā tata nei, i whakaputaina e te British Journal of Clinical Pharmacology te aratohu haumanu tuatahi i whakawhanakehia e te UK Centre of Excellence for Regulatory Science and Innovation in Pharmacogenomics (CERSI PGx), ko te taitara "CYP2C19 genotype testing for clopidogrel: He aratohu i whakawhanakehia e te UK Centre of Excellence for regulatory science and innovation in pharmacogenomics (CERSI PGx)". E arotahi ana tēnei tuhinga tohu nui ki te uara haumanu o te CYP2C19 genotyping i roto i te ārahi i te rongoā clopidogrel.
Mō CERSI PGx
Ko CERSI PGx tētahi o ngā pokapū pūtaiao me te auahatanga ture e whitu i tautokona e te kāwanatanga o te UK i whakarewahia i te marama o Hānuere 2025. E arahina ana e te Whare Wānanga o Liverpool, e tautokona tahitia ana e Innovate UK, te Medical Research Council (MRC), te Medicines and Healthcare products Regulatory Agency (MHRA), me te Office for Life Sciences (OLS). Ko te whāinga o te pokapū he whakatere i te whakaurunga haumaru me te whai hua o te pharmacogenomics (PGx) ki roto i te National Health Service (NHS) mā te aro atu ki ngā arai matua o te whakatinanatanga. Ko tēnei aratohu te aratohu haumanu tuatahi i tukuna mai i te wā i whakatūria ai a CERSI PGx.
He aha te hiranga o te CYP2C19 mō te Clopidogrel
Ko te CYP2C19 tētahi mema matua o te whānau whākōkī cytochrome P450, e kawenga ana mō te whakahohenga, te whakakorenga rānei i te maha o ngā rongoā. Nā ngā momo ira i roto i te CYP2C19 ka rerekē te pākia o te rongoā i waenga i ngā tāngata takitahi, ka pā ki te whai huatanga me te haumaru.
He rongoā antiplatelet whānuitia te Clopidogrel hei ārai i ngā mate toto toto i roto i te mate uaua coronary, te whiu ischaemic, te mate uaua peripheral, me te atrial fibrillation. Hei prodrug, me whakahohe te clopidogrel i te pākia e CYP2C19. E whakarōpūhia ana e te aratohu ngā tāngata takitahi ki ngā ultra-tere, tere, noa, waenga, me ngā metabolizer ngoikore i runga i te momoira CYP2C19. Kāore e taea e ngā kaikawe o ngā ira ngaro o te mahi (hei tauira, CYP2C192 me *3*) – ngā metabolizer waenga me ngā metabolizer ngoikore – te whakahohe tika i te clopidogrel, ka hua ake te korenga o te aukati i ngā pereti toto me te pikinga o te mōrearea o te thrombosis anō.
Ko te auau o te ira CYP2C192 e tata ana ki te 15% i roto i ngā tāngata o Ūropi, 30% i roto i ngā tāngata o Āhia ki te Tonga, ā, tae atu ki te 60% i roto i ngā taupori taketake o te Moana-nui-a-Kiwa.
Taunakitanga Matua: Whakamātautau CYP2C19 Whānui mō te Clopidogrel
E mea ana te aratohu, ahakoa te tohu, me whiwhi ngā tūroro katoa e whakaarohia ana mō rātou te clopidogrel i te rongoā.CYP2C19te whakatauira ira tangata.I runga i ngā hua, me whakapai ake te rongoā antiplatelet:
-Ngā kaiwhakaora ngoikoreme karo i te clopidogrel, me te whakamahi i ngā rongoā rerekē kāore e whakawhirinaki ki te pākia o te CYP2C19, pērā i te ticagrelor, te prasugrel rānei.
-Ngā kaiwhakaora waengame whai whakaaro hoki ki ētahi atu rongoā rerekē, ki ngā tikanga rongoā kua whakarerekētia rānei, kaua e whakanui noa i te horopeta o te clopidogrel.
I te UK, kua whakaaetia te clopidogrel mō te ārai tuarua i ngā mate atherothrombotic, mō te whakaeke ischaemic transient (TIA) mōrearea ki te nui, te whiu ischaemic ngāwari rānei, me te ārai i ngā mate atherothrombotic me te thromboembolic i roto i te atrial fibrillation.
I tua atu i te Clopidogrel: Ētahi atu Rongoā he mea nui te whakatauira ira CYP2C19
Ko te hiranga o te ira-ira CYP2C19 he nui atu i te clopidogrel. Hei whākōkī matua e whakapūmau ana i te rongoā, he mahi nui anō hoki tā CYP2C19 i roto i te whakapūmautanga o te voriconazole, ētahi rongoā ārai-pōrearea, me ngā aukati papu proton (PPI). He maha ngā aratohu ā-ao me ā-motu e taunaki ana i te whakawhaiaro ira-ira mō ēnei rongoā.
1. Ngā rongoā ārai pouri (SSRI)
Ko ngā aukati tango serotonin whiriwhiri (SSRI) – pērā i te sertraline, citalopram, me te escitalopram – ngā rongoā tuatahi mō te pouri, ā, ka whakapūmautia e te CYP2C19. Ko te mahi a te whākōkī CYP2C19 te mea e whakatau tika ana i te kukū o ēnei rongoā i roto i te toto. Ko ngā kaiwhakapūmau ngoikore he whakahekenga 30%–60% i roto i te whakakorenga rongoā, ka pāngia rātou e ngā pānga kino pērā i te roa o te wā QT me te whakamoe. He maha ngā wā ka iti ake te kukū o ngā kaiwhakapūmau ultrarapid i roto i te toto, ka roa ai te urupare maimoatanga me te nui ake o te mōrearea o te whakamutu i te rongoā.
E ai ki te aratohu 2023 Clinical Pharmacogenetics Implementation Consortium (CPIC) he nui ake te mōrearea o te roanga o te QT mō ngā tāngata ngoikore te metabolism e tango ana i te citalopram, i te escitalopram rānei, ā, e taunaki ana kia whakaitihia te horopeta 50%. E tohutohu ana te aratohu 2021 Dutch Pharmacogenetics Working Group (DPWG) me whakaitihia te horopeta mōrahi o te escitalopram mō ngā tāngata ngoikore te metabolism mā te 50%, ā, me karo katoa ngā tāngata tere rawa i te escitalopram. Mō te sertraline, e taunaki ana te DPWG kia kaua e neke atu i te 75 mg te horopeta o ia rā mō ngā tāngata ngoikore te metabolism.
He mea nui, ko te Chinese Expert Consensus on Pharmacogenomic Testing in Psychiatry (2025) i whakaputaina tata nei – i whakawhanakehia e te Precision Medicine Collaboration Group o te Chinese Society of Psychiatry – kei roto ngā taunakitanga mō te ira-ira CYP2C19. E kī ana te tauākī whakaae ka taea te tohutoro i ngā taunakitanga whakarerekētanga horopeta mai i ngā aratohu o te ao pēnei i te CPIC me te DPWG mō ngā whākōkī e whakapūmau ana i te rongoā (tae atu ki te CYP2C19) mō ngā taupori Hainamana. Nō reira, ko te ira-ira CYP2C19 i mua i te tīmatanga o te rongoā SSRI (hei tauira, escitalopram) ka taea te arotau i te horopeta, te huri rānei ki ngā rongoā rerekē kāore i whakapūmautia e te CYP2C19, ā, nā reira ka tutuki te maimoatanga tika, ka whakapai ake i ngā reiti urupare, ka whakaiti i ngā pānga kino.
2. Ngā Ārai Papu Pūtorino (PPI)
Ko ngā aukati papu proton – tae atu ki te omeprazole, te lansoprazole, me te pantoprazole – e whakamahia whānuitia ana mō ngā mate e pā ana ki te waikawa pērā i te mate reflux gastroesophageal me ngā mate puku. He tino whakawhirinaki hoki tō rātou pākia ki te CYP2C19. Ko ngā tūroro he rerekē ngā momoira CYP2C19 e whakaatu ana i te rerekētanga nui i roto i te urupare ki ngā PPI. Ko ngā kaikawe o ngā ira ngaro o te mahi (*2, *3) kua tino piki ake te whakaaturanga rongoā, ka whakanui ake pea i te pehi waikawa engari ka whakapiki ake hoki i te mōrearea o ngā pānga kino. He rerekē, he iti ake te kukū plasma o ngā kaiwhakaora noa, ā, ka ngoikore ake pea te pehi waikawa, ahakoa he nui tonu te rerekētanga i waenga i ngā tāngata takitahi.
E tohutohu ana te aratohu CPIC 2020 mō ngā PPI kia tere rawa te mimiti o te rongoā e ngā kaiwhakaora tere rawa e tango ana i te omeprazole, i ngā rongoā rite rānei, ā, ka hua ake he koretake o te kukū o te toto, ā, he ngoikore te pehi waikawa. Mō ēnei tūroro, me whakanui ake te horopeta, me te aroturuki i te urupare rongoā. Mō ngā kaiwhakaora ngoikore, he puhoi te whakakorenga o te rongoā, ā, ka piki ake pea te kukū o te toto; ahakoa he pai ake te whai huatanga, ka piki ake te kaha o te paitini o te rongoā. He mea tika te whakaiti i te horopeta me te aroturuki i te urupare. Nō reira, mō ngā tūroro e tīmata ana i te rongoā PPI, mō te hunga rānei e pāngia ana e te urupare ngoikore, ngā pānga kino rānei, e taunakihia ana te whakatauira ira CYP2C19 hei ārahi i te horopeta takitahi, te arotau i te whai huatanga, me te whakaiti i ngā pānga kino.
3. Voriconazole
He rongoā harore whānui te Voriconazole e whakamahia ana hei rongoā i ngā mate harore kino pērā i te aspergillosis urutomo. He whaiti te matapihi rongoā: ka nui rawa ngā kukū toto i roto i te toto ka nui ake te tūponotanga o te paitini o te ate me ngā raruraru tirohanga, engari ka kore e angitu te maimoatanga i roto i ngā kukū iti. Ko te CYP2C19 te pūtake o te pākia o te voriconazole, ā, he nui te pānga o ngā momo ira ki tōna kukū toto.
I whakaputa te CPIC i tētahi aratohu motuhake mō te CYP2C19 me te voriconazole i te tau 2016. E kī ana ko ngā kaiwhakaora tere rawa kua whakaiti i te kukū o te voriconazole, ā, he maha ngā wā kāore e eke ki ngā taumata rongoā e hiahiatia ana. Ko ngā kaiwhakaora ngoikore he kukū teitei ake, ā, he nui ake te mōrearea o ngā tauhohenga kino. E whakarato ana te aratohu CPIC i ngā taunakitanga horopeta motuhake i runga i te momoira. Hei tauira, me whiwhi ngā kaiwhakaora tere rawa pakeke i ngā rongoā raina tuatahi rerekē kāore e whakawhirinaki ki te metabolism CYP2C19, pērā i te isavuconazole, te amphotericin B liposomal, te posaconazole rānei. Nō reira, mā te whakarōpūtanga momoira CYP2C19 i mua i te rongoā voriconazole ka taea te horopeta takitahi, ā, ka whakaitihia te auau o ngā tauhohenga kino e pā ana ki te rongoā.
Te Hiranga Hauora: Te Whakapūmau i te Pono o te Rongoā
Ko te aratohu hou kua tukuna nei ka whakanoho anō i te iraira CYP2C19 ki mua i te ao rongoā tika. Heoi, he mea nui kia mōhiotia ko ngā tono haumanu o te iraira CYP2C19 he nui atu i te clopidogrel – mai i te voriconazole (rongoā ārai harore) me ngā SSRI (rongoā ārai pouri) ki ngā aukati papu proton hei pehi i te waikawa. Ko te iraira CYP2C19 he "kāpehu" mō te rongoā.
I te mea e whānui haere ana te whakaaetia o te rongoā tika, kei te piki haere te maha o ngā aratohu whai mana e whakauru ana i te ira CYP2C19 ki ngā tukanga rongoā o ia rā. Mō ngā tūroro, mā te mōhio ki ō rātou ake ira CYP2C19 ka āwhina i a rātou ki te mārama ki tā rātou ake urupare rongoā, ā, ka taea ai te whakatau tahi me tā rātou tākuta ki te whakawhanake i tētahi mahere maimoatanga e tika ana. Mō ngā tākuta, ko te whakauru i ngā hua whakamātautau ira tūturu ki ngā whakataunga whakahaunga he huarahi kaha ki te whakapai ake i te kounga maimoatanga me te whakarite i te haumaru o te tūroro.
Whakamātautau-Makro me te Moroiti'sOtinga Tātaritanga Ira CYP2C19
Kei te Macro & Micro Test tētahi kete ira CYP2C19 e hangai ana ki tētahi pūnaha whakarerekētanga ātete-whakarei ake (ARMS) kua honoa ki ngā whakamātautau Taqman me ngā āhuatanga e whai ake nei:
-Kapinga whānui o te ira– kiteaCYP2C192, *3, me *17me te kore e ngaro ngā momo matua.
-Te mana whakahaere kounga pakari– kei roto ngā mana whakahaere kino/pai, he mana whakahaere ā-roto, me te whākōkī UDG mō ngā taumata mana whakahaere kounga e whā hei whakarite i ngā hua tika.
-Tango aunoa– e hototahi ana ki te mīhini tango waikawa karihi aunoa katoa a Macro & Micro-Test, e whakapai ake ana i te pai o te rere o te mahi.
-Hototahi whānui– ka mahi tahi me ngā taputapu PCR wā-tūturu rongonui o te mākete, tae atu ki te ABI 7500 Hongshi SLAN 96P.
-Whakamāoritanga hua aunoa– mā te pūmanawa tātari motuhake (i runga i te ABI 7500, SLAN 96P, me ētahi atu) ka taea te whakamaori aunoa i ngā hua, ka whakarei ake i te whai huatanga.
-Aunoatanga rite mō te POCT– Mā te HWTS AIO800 Fully Automated Nucleic Amplification Analyzer ka taea te mahi "tāuru tauira, whakaputa hua".
I te haere tonu o te whanaketanga o te pharmacogenomics, e matapaetia ana ka whai hua te ira-ira CYP2C19 ki te piki haere o te maha o ngā tūroro, ka nekehia te rongoā tika mai i te ariā ki te mahi haumanu noa. Ko te aratohu CERSI PGx hou kua whakaputaina e whakakaha ana i te tūranga nui o te whakamātautau CYP2C19 ehara i te mea mō te clopidogrel anake engari mō te rārangi rongoā e tipu haere ana, tae atu ki ngā antidepressants, ngā aukati papu proton, me te voriconazole. Hei whakahaere i te whakamahinga whānui o te whakahaunga ira-ira, he mea nui ngā otinga whakamātautau pono me te ngāwari ki te whakamahi. Ko te kohinga whakamātautau pharmacogenomic a Macro & Micro-Test, e whakaatu ana i te kapinga allele whānui, te mana kounga pakari, me ngā tūāpapa aunoa, e whai ana ki te tautoko i ngā kaiwhakarato hauora ki te whakatinana i te rongoā tika me te tiaki i te hauora o te tūroro.
Ngā Hua e Pā Ana:
Ngā Tohutoro:
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2.Lee CR, Luzum JA, Sangkuhl K, et al. Aratohu Whakatinanatanga o te Clinical Pharmacogenetics mō te CYP2C19 Genotype me te Clopidogrel Thermal: Whakahōu 2022. Clin Pharmacol Ther. 2022. doi:10.1002/cpt.25261.
3. Te Whare Wānanga ā-Motu mō te Hiranga Hauora me te Tiaki (NICE). Te whakamātautau iraira CYP2C19 hei ārahi i te whakamahinga o te clopidogrel i muri i te whiu ischaemic, i te whakaeke ischaemic poto rānei. Aratohu tātaritanga DG59. I whakaputaina: 31 Hōngongoi 2024.
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7.Bousman CA, Stevenson JM, Ramsey LB, et al. He Aratohu mō te Clinical Pharmacogenetics Implementation Consortium (CPIC) mō ngā Ira-ira CYP2D6, CYP2C19, CYP2B6, SLC6A4, me te HTR2A me ngā Rongoā Whakaiti i te Aroturukitanga o te Serotonin. Clin Pharmacol Ther. 2023;114(1):51-68. doi:10.1002/cpt.2903.
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Wā tuku: Paenga-whāwhā-22-2026