Pharmacokinetics mukurapa kwevarwere vechipatara
Pharmacokinetics inyaya yekudzidza kuti mishonga inofamba sei mumuviri kubva panguva yainopinda mumuviri kusvika yabviswa zvachose. Mukurapa muzvipatara, kunzwisisa pharmacokinetics inyaya yakakosha yekuona kuti varwere vanowana kurapwa kunoshanda uye kwakachengeteka. Izvi zvinodaro nekuti varwere vari muchipatara vanowanzova nematambudziko akaomarara: kusashanda zvakanaka kweitsvo kana chiropa, kukwegura, shanduko mumvura yemuviri, kurwara zvakanyanya, uye kushandiswa kwemishonga yakawanda (polypharmacy). Zvese izvi zvinogona kuchinja maitiro emuviri kumishonga uye kuwedzera njodzi yekukundikana kwekurapwa uye migumisiro yakaipa.
Kazhinji, pharmacokinetics inosanganisira maitiro mana makuru anozivikanwa seADME: kunyudzwa, kugoverwa, metabolism, uye kubviswa. Maitiro mana aya anoona huwandu hwemushonga muropa nematishu nekufamba kwenguva. Muzvipatara, chiyero chemushonga uye nguva dzekuunzwa kwemushonga zvinowanzo fanirwa kugadziriswa zvichienderana ne pharmacokinetics, kunyanya kune mishonga ine huwandu hwakamanikana hwekurapa senge aminoglycosides, vancomycin, digoxin, lithium, uye mamwe ma anticoagulants.
1. Kunyudzwa: Kunoita kuti mushonga upinde zvakanaka
Kumwisa mushonga inzira iyo mushonga unopfuura nayo kubva panzvimbo yaunopinzwa uchienda muropa. Muvarwere vari muchipatara, nzira dzekupa mushonga dzinosiyana-siyana, dzinosanganisira kunwa, kupinzwa mutsinga (IV), kupinzwa mutsinga (IM), kupinzwa mutsinga pasi peganda, uye nzira dzakagadzirwa dzakadai sekufemereka kana kupinzwa mutsinga. Muvarwere vanorwara zvakanyanya, nzira yekupinda mutsinga inowanzo sarudzwa nekuti inopa mhedzisiro nekukurumidza uye inodzivirira zvipingamupinyi zvekupinzwa.
Zvisinei, kunwa nemuromo muvarwere vari muchipatara kazhinji hakuna kunaka. Zvinhu zvakaita sekusvotwa, kurutsa, kutadza kufamba zvakanaka kwemudumbu, kushandiswa kwemishonga inoderedza acid, kana kudya kunovaka muviri zvinogona kuchinja kunwa kwemushonga. Semuenzaniso, mamwe maantibiotic anogona kusunganidza kune zvicherwa zviri muchikafu kana mukaka, zvichideredza kunwa kwawo. Muvarwere vane nasogastric tubes, mimwe mishonga (semuenzaniso, mishonga inosunungurwa kwenguva refu) haifanirwe kupwanywa nekuti izvi zvinogona kukonzera kuburitswa kwemushonga nekukurumidza uye kuwedzera njodzi yekukuvadzwa.
Pamusoro pezvo, kuyerera kweropa mumasero emuviri kuvarwere vane shock kunogona kuderedza kunwa kwemishonga ye IM kana iri pasi peganda. Izvi zvinoita kuti vanachiremba vasarudze nzira ye IV kuti vave nechokwadi chekuti mushonga wakapihwa unotorwa nguva dzose uye zvakakwana.
2. Kugoverwa: Basa reHuwandu hweKugoverwa muKutarisirwa kweVarwere Vari Muchipatara
Kuparadzirwa kwemishonga kubva muropa kuenda munhengo dzemuviri. Kuparadzirwa kwemishonga kunokonzerwa nekuyerera kweropa kuenda kunhengo dzemuviri, kubatana kwemishonga nemapuroteni eplasma (kunyanya albumin), uye kuumbwa kwemvura mumuviri nemafuta. Muzvipatara, shanduko mumamiriro emuviri wemurwere dzinogona kuchinja zvakanyanya maitiro ekugoverwa kwemishonga.
Pfungwa huru mukugoverwa kwemishonga ihuwandu hwekugoverwa kwemishonga (Vd), iyo "huwandu hunoonekwa" hunotsanangura kuti mushonga unopararira zvakadii mumatishu. Muvarwere vane kuzvimba, sepsis, kana huwandu hwakawanda hwemvura, huwandu hweVd hwemishonga inonyungudika mumvura (hydrophilic) hunogona kuwedzera. Izvi zvinogona kutungamira kuhuwandu hwemishonga hushoma pane hunotarisirwa kana mushonga wekutanga usina kugadziriswa. Saka, mune dzimwe nguva, huwandu hwemushonga hunodiwa kuti uwane huwandu hwekurapa nekukurumidza.
Kusunga mapuroteni kwakakoshawo zvikuru. Kune varwere vane hypoalbuminemia (semuenzaniso, avo vane kushaya chikafu chakakwana, chirwere chechiropa, kana zvirwere zvakakomba), chikamu chemushonga chinowedzera. Zvisinei, chikamu chemushonga ndicho chikamu chinoshanda mumishonga uye chinogona kukonzera chepfu. Semuenzaniso, mushonga unobatanidzwa zvakanyanya nealbumin, senge phenytoin, unogona kuva nehupfu hwakanyanya pahuwandu hwese "hunoratidzika kunge hwakajairika" kana albumin yakaderera. Nokudaro, kududzirwa kwehuwandu hwemushonga muropa kunofanirwa kufunga nezvemamiriro ezvinhu ekiriniki.
3. Kuchinja Kwemuviri: Chiropa Senzvimbo Yekushandura Mishonga
Kugayiwa kwemuviri, kunyanya muchiropa, kunoshandura mishonga kuita mafomu anobviswa zviri nyore. Ma enzymes echiropa akadai se cytochrome P450 (CYP) anoita basa guru mukuita uku. Muzvipatara, gayiwa kwemuviri kunogona kuchinjwa nekuda kwechirwere chechiropa, kutadza kushanda kwemoyo, sepsis, kana kushandiswa kwemimwe mishonga inodzivisa kana kukonzera ma enzymes egayiwa.
Kudyidzana kwemishonga inyaya huru. Mishonga inodzivirira maCYP inogona kuwedzera huwandu hwemimwe mishonga, zvichiwedzera njodzi yekukuvadzwa. Kusiyana neizvi, zvinhu zvinokurudzira ma enzyme zvinogona kuderedza huwandu hwemishonga uye zvinokonzeresa kutadza kurapwa. Varwere vari muchipatara vanowanzo gamuchira mishonga yakawanda panguva imwe chete, yakadai semishonga inorwisa mabhakitiriya, mishonga inouraya fungus, mishonga inorwisa pfari, uye mishonga yemwoyo, zvichiwedzera njodzi yekudyidzana.
Uyezve, metabolism inosanganisirawo mishonga inorwisa utachiona, inova mishonga inofanira kumutswa nemuviri. Kana kushanda kwechiropa kukanganisika, kushandiswa kwemishonga inorwisa utachiona kungave kusina kunaka, zvichiita kuti kurapwa kusashande zvakanaka. Mumamiriro ezvinhu akadaro, kusarudza mimwe mishonga kana kugadzirisa madhigirii kunova kwakakosha.
4. Kubvisa: Kiyi Yekugadzirisa Dose MuItsvo Dzakakanganisika
Kubvisa mishonga mumuviri, kunyanya kuburikidza neitsvo uye mimwe kuburikidza nenyongo. Muzvipatara, kushanda kweitsvo kunowanzo kuve chinhu chikuru chinotarisirwa nekuti mishonga yakawanda inoburitswa muweti. Muvarwere vane chirwere cheitsvo chakakomba kana chisingaperi, mishonga inogona kuungana uye kukonzera migumisiro yakaipa kana mushonga wacho usina kugadziriswa.
Kugadziriswa kwemushonga kunowanzoenderana nefungidziro yekuti glomerular filtration rate (eGFR) kana kuti creatinine clearance (CrCl). Zvisinei, muvarwere vanorwara zvakanyanya, huwandu hwecreatinine hunogona kusagadzikana, zvichiita kuti kuverenga kwe clearance kusanyatsojeka. Saka, kutarisa kwekiriniki zvakanyanya uye, kana zviripo, kutarisa mishonga yekurapa (TDM) inzira dzakakosha.
Muvarwere vari kurapwa nehemodialysis kana kuti continuous renal replacement therapy (CRRT), pharmacokinetics yemishonga yakawanda inochinja zvikuru. Mimwe mishonga inogona kudirwa ropa inorasika panguva yekuvhiyiwa, zvichiita kuti pave nekuwedzera dose kana kugadziriswa kwepurogiramu. Sarudzo iyi inowanzo tarisa saizi yemamorekuru emushonga, kubatana kwemapuroteni, Vd, uye hunhu hwedialysis membrane.
MaParamende Akakosha ePharmacokinetic muKurapwa Kwechipatara
Zvimwe zvinhu zvakakosha zvinoshandiswa kutungamira kurapwa zvinosanganisira:
1. Kuwanikwa kwemushonga (F): chiyero chemushonga unosvika pakuyerera kweropa mumuviri. Zvakakosha pakuchinja kubva muIV kuenda kunzira yemuromo.
2. Kubvisa mushonga (Cl): kugona kwemuviri kubvisa mushonga. Kunotsvaga kuti mushonga wacho unofanira kuchengetwa zvakanaka here.
3. Hafu yehupenyu (t½): nguva inodiwa kuti huwandu hwemushonga huderere nehafu. Inoona nguva yekushandiswa kwemushonga uye nguva yekusvika padanho rakadzikama.
4. Kugara kwenguva refu: mamiriro ezvinhu apo huwandu hwemushonga hunopinda hunoenderana nehuwandu hunobuda, hunowanzo kuwanikwa mushure mehafu yehupenyu hwemunhu anenge afa kwe4-5.
5. AUC (Nzvimbo Iri Pasi Pechinotenderera): Kushandiswa kwemishonga yese kwenguva yakatarwa. Inowanzo shandiswa pamishonga yekuuraya utachiona kuti ione kushanda kwayo.
Kunzwisisa zvinhu izvi kunobatsira vanachiremba kugadzirisa marapirwo, semuenzaniso nguva yekupa mushonga wekutakura, kuti mushonga wekuchengetedza chii, uye nguva yakakodzera yekuyera huwandu hwemushonga.
Kutarisa Mishonga Yekurapa (TDM): Kuchengetedza Kushanda Uye Kuchengetedzeka
TDM ndiyo nzira yekuyera huwandu hwemishonga muropa kuti kurapwa kuve nyore. Muzvipatara, TDM inonyanya kubatsira mishonga ine huwandu hushoma hwemishonga, mishonga ine musiyano mukuru wemishonga pakati pevarwere, kana varwere vane mamiriro ezvinhu anochinja nekukurumidza.
Muenzaniso weTDM ivancomycin, uko kubatwa kwacho kunowanzo ongororwa uchishandisa nzira yeAUC/MIC. Kuongororwa uku kunoita kuti mushonga uyu ushande zvakanaka pakuuraya mabhakitiriya asi haukonzeri kukuvadza kwemasero matsvuku. TDM inowanzoshandiswawo nemaaminoglycosides kudzivirira kukuvadza kwemasero matsvuku uye kukuvara kweitsvo, uye nemishonga inorwisa pfari yakaita sephenytoin kudzora pfari pasina kunyaradza kana kukuvadza.
Zvisinei, TDM inofanira kuitwa nemazvo: nguva yekutora sampuli, kududzirwa kwemhedzisiro, uye kugadziriswa kwemushonga kunofanirwa kutariswa nemamiriro emurwere uye parameters yemishonga.
Pharmacokinetics muVanhu Vakakosha muZvipatara
Mamwe mapoka evarwere anoda kutarisirwa kwakakosha:
– Varwere vakwegura: vanowanzova nedambudziko rekushanda kweitsvo, shanduko muchimiro chemuviri (mafuta akawanda, mvura shoma), uye njodzi yakakura yekushandiswa kwemishonga.
– Vana nevarwere vacheche: mashandiro enhengo dzemuviri haana kusimba, zvichikonzera kunonoka kana kusagadzikana kwemetabolism uye kubviswa kwayo; chiyero chinofanira kuenderana nehuremu hwemuviri uye nhanho yekukura.
– Varwere vakafuta: shanduko muVd uye kubviswa kweropa zvinogona kuita kuti dosing yakajairika isanyatsojeka; kusarudza huremu hunotarisirwa (chaihwo, hwakakodzera, kana hwakagadziriswa) kwakakosha.
– Varwere vane dambudziko guru (ICU): sepsis, kushandiswa kwevasopressor, uye shanduko mumvura yemuviri zvinogona kukurumidza kuchinja kupinza, kupararira, uye kubviswa kweropa.
Mhedziso
Pharmacokinetics chinhu chakakosha pakurapa varwere muchipatara nekuti inobatsira kufanotaura nekudzora huwandu hwemishonga mumuviri. Nekunzwisisa kunyudzwa, kugoverwa, kugadzirwa kwemetabolism, uye kubviswa kwayo, nyanzvi dzehutano dzinogona kugadzirisa madosi zvakanyatsonaka, kudzivirira chepfu, uye kuvandudza kushanda kwekurapa. Muchipatara—kunyanya kune varwere vane mamiriro akaomarara—kushandiswa kwe pharmacokinetics uye TDM inzira yakakosha yekuwana kurapwa kwakarongeka, kwakachengeteka, uye kunoshanda.
Kana muchida, ndinogona kugadzirisa chinyorwa ichi kuti chienderane nepepa resainzi (rine magwaro/mabhuku), kana kuwedzera mienzaniso yezviitiko zvekiriniki (semuenzaniso, kugadzirisa madosi evancomycin muvarwere vane dambudziko reitsvo).
