Lub tswv yim tsim qauv ntawm Nonclinical Pharmacokinetic Studies: Los ntawm ADME Profiling rau Kev Txiav Txim Siab Txhais Lus -Ua

Tsis khoPharmacokinetics (PK)Cov kev tshawb fawb ua lub luag haujlwm tseem ceeb hauv kev txhim kho tshuaj los ntawm kev qhia txog kev ua yeeb yam li cas hauv vivo. Los ntawm ob qho tib si hauv vitro thiab tsiaj kev tshawb fawb, PK kev tshawb nrhiav txhais cov txheej txheem ntawm kev nqus, kev faib tawm, cov metabolism, thiab kev tso tawm (ADME), ua rau kev kwv yees ntawm qhov tseem ceeb xws li raug, tshem tawm, thiab bioavailability.

Ib qho zoo -tsim PK lub tswv yim tsis yog qhov tseem ceeb rau kev ua raws cai nkaus xwb tab sis tseem ceeb heev rau kev txhais lus ua tiav, txhawb kev xaiv koob tshuaj, kev ntsuam xyuas kev nyab xeeb, thiab kev sim tshuaj ntsuam xyuas.

Kev xaiv cov tsiaj txhu tsim nyog yuav tsum ua qhov tseem ceeb ntawm kev txhais lus cuam tshuam rau tib neeg cov tshuaj pharmacokinetics thaum tswj kev sib raug zoo nrog kev tshawb fawb toxicology thiab pharmacology.

Rau kev kho tshiab, kev tswj hwm kev cia siab feem ntau yuav tsum muaj tsawg kawg yog ob hom: ib tus nas (feem ntau nas) thiab ib qho tsis yog - nas (xws li dev, minipig, lossis tsis yog - tib neeg primate). Ntawm cov no, tsis yog -tib neeg primates (NHPs) feem ntau nyiam vim lawv qhov ze zog ntawm lub cev thiab metabolic zoo sib xws rau tib neeg.

Qhov twg ua tau, PK cov kev tshawb fawb yuav tsum tau ua nyob rau hauv cov tsiaj tsis nco qab nrog cov serial sampling los ntawm tib tus neeg. Txoj hauv kev no txo ​​cov kev sib tshuam ntawm -tsiaj hloov pauv thiab txhim kho cov ntaub ntawv zoo.

Cov kev xav ntawm kev tshawb fawb tsim muaj xws li:

• Sib npaug sib deev faib tshwj tsis yog chaw kho mob tsim nyog lwm yam
• Kev suav ntawm ob qho tib si niam txiv compound thiab cov metabolites loj
• Tsim nyog tus qauv loj los xyuas kom muaj zog concentration-lub sij hawm nkhaus kev tsim kho

Ib leeg -Kev Kawm Tshuaj

Ib zaug - koob tshuaj PK kev tshawb fawb feem ntau suav nrog tsawg kawg peb koob tshuaj:

• Cov koob tshuaj tsawg ze ntawm qhov tsawg kawg nkaus
• Nruab nrab thiab siab koob tshuaj scaled proportionally

Lub hom phiaj yog los txiav txim seb cov tshuaj pharmacokinetics puas yog linear lossis nonlinear thoob plaws qhov kev sim.

Ntau -Kev Kawm Tshuaj

Rau cov tebchaw uas npaj rau kev tswj hwm tsis tu ncua lossis muaj peev xwm sib sau ua ke, rov ua dua - cov kev tshawb fawb PK yog xav tau.

Dose regimen tsim yuav tsum tau coj los ntawm:

• Tshem tawm ib nrab-lub neej (t₁/₂)
• Pharmacodynamic teebmeem
• Predicted soj ntsuam lub sij hawm noj tshuaj

Hla- hom tshuaj txhaj tshuaj ntxiv tuaj yeem ua tau siv lub cev qhov chaw thaj chaw normalization lossis raug-raws li kev ntsuas.

Txoj hauv kev ntawm kev tswj hwm hauv kev tshawb fawb PK uas tsis yog kev kho mob yuav tsum, thaum twg ua tau, phim txoj hauv kev kho mob.

Cov txheej txheem muaj xws li:

• Intravenous kev tswj hwm rau kev bioavailability thiab kev soj ntsuam kev tshem tawm
• Extravascular txoj kev (xws li, qhov ncauj, inhalation) kom muaj kev cuam tshuam kev siv tshuaj kho mob

Rau kev txhaj tshuaj ntawm qhov ncauj, gavage yog siv dav, txawm hais tias hom -kev txiav txim siab tshwj xeeb (xws li, luav) yuav tsum raug coj mus rau hauv tus account. Kev yoo mov ua ntej noj tshuaj feem ntau pom zoo kom txo qis kev hloov pauv hauv kev nqus tshuaj.

Kev txheeb xyuas cov tshuaj thiab cov tshuaj metabolites hauv cov tshuaj lom neeg yog ib qho tseem ceeb ntawm PK kev tshawb fawb.

Niaj hnub nimno bioanalysis cia siab rau siab -rhiab heev thiab siab - cov txheej txheem tshwj xeeb, tshwj xeeb tshaj yog:

• LC-MS/MS raws li tus qauv kev lag luam
• Cov txheej txheem ntxiv xws li HPLC, GC, lossis radiolabeling qhov tsim nyog

Kev lees paub txoj hauv kev yuav tsum ua raws li cov txheej txheem kev cai tam sim no, nrog rau kev ua raws li ICH M10 (2022) cov qauv, kom ntseeg tau tias:

• Selectivity, rhiab heev, raug thiab precision, ruaj khov

Ib qho qauv tsim qauv zoo yog qhov tseem ceeb los txheeb xyuas qhov tseeb-lub sijhawm profile.

Cov ntsiab cai tseem ceeb suav nrog:

• Ua ntej - koob tshuaj sampling los tsim cov hauv paus
• Kev ntsuas ntom ntom ntawm qhov siab tshaj plaws (Cmax)
• Kev pab them nqi ntawm kev nqus, kev faib tawm, thiab kev tshem tawm theem
• Tag nrho lub sij hawm ncua mus rau 3-5 ib nrab-nyob los yog kom txog thaum cov concentrations poob qis dua 5-10% ntawm Cmax

Kev sau ntshav ntim yuav tsum nyob twj ywm nyob rau hauv cov kev txwv ntawm lub cev kom ntseeg tau tias tsiaj noj qab haus huv thiab cov ntaub ntawv ntseeg tau.

PK tsom xam tsim cov ntsiab lus tseem ceeb uas piav qhia txog kev siv tshuaj:

Rau kev tswj hwm txoj hlab ntshav: Ib nrab -lub neej (t₁/₂), Volume of distribution (Vd), Clearance (CL), Area under curve (AUC).

Rau kev tswj hwm cov hlab ntsha: Cmax thiab Tmax, Bioavailability, Mean residence time (MRT).

Ob tus neeg thiab pab pawg- cov ntaub ntawv qib yuav tsum tau tshaj tawm, suav nrog kev ntsuas qhov sib txawv thiab cov duab sawv cev.

Rov ua dua -cov kev tshawb fawb koob tshuaj yuav tsum tau soj ntsuam ntxiv: Tsis tu ncua- lub xeev raug, Qhov sib npaug sib npaug, Qhov sib txawv ntawm thawj koob thiab zaum kawg.

Tshaj li qhov kev kwv yees kwv yees, cov kev tshawb fawb PK uas tsis yog kev kho mob ua tus choj ntawm kev tshawb pom thiab kev kho mob. Kev koom ua ke nrog cov tshuaj pharmacodynamics (PK/PD), toxicology, thiab biomarker cov ntaub ntawv ua kom paub txog kev txiav txim siab - ua rau: Ua ntej - hauv - kev xaiv tib neeg koob tshuaj, kev kwv yees qhov rai, kev pheej hmoo txo ​​cov tswv yim.

Ntawm Prisys Biotech, nonclinical pharmacokinetics tsis raug kho raws li kev ua haujlwm cais tab sis yog ib qho tseem ceeb ntawm kev txhais lus science.

Nrog rau ntau tshaj 15 xyoo ntawm kev paub nyob rau hauv tsis yog -tib neeg primate kev tshawb fawb thiab ib tug tag nrho kev koom ua ke platform, Prisys muab xaus- mus rau -kawg PK cov kev daws teeb meem raws li complex tshuaj modalities, xws li biologics, noob kev kho mob, thiab CNS- cov hom phiaj kho mob.

Cov peev txheej tseem ceeb muaj xws li:

• Advanced NHP Qauv:Cynomolgus liab qauvnrog rau kev txhais lus siab rau PK / PD, tshwj xeeb tshaj yog nyob rau hauv CNS, kev tiv thaiv kab mob, thiab cov kab mob ua pa.
• Kev kho mob-Qib Kev Sib Koom Tes: MRI, CT, thiab PET- cov platforms ua kom muaj txiaj ntsig tiag tiag - lub sijhawm soj ntsuam ntawm kev faib tshuaj thiab cov phiaj xwm kev koom tes.
• Comprehensive Bioanalysis thiab Sampling: Kev sib xyaw ua haujlwm los ntawm kev siv tshuaj rau kev sau cov qauv, bioanalysis, thiab kev txhais cov ntaub ntawv.
• Kev txhais lus-Kev tshawb fawb-Center(PTRC): Lub ntiaj teb -chaw chaw txhawb nqa PK, kev nyab xeeb tshuaj, thiab tib neeg-zoo li kev kawm tsim qauv raws li AAALAC- cov qauv kev lees paub.
• Customized Study Design: Cov kev cai yooj yim ua raws li cov neeg siv khoom-cov kev cai tshwj xeeb thiab cov hom phiaj kev tshawb fawb.

Los ntawm kev sib txuas cov tshuaj pharmacokinetics nrog cov qauv kab mob, kev kos duab, thiab cov tswv yim biomarker, Prisys txhim kho tus nqi kwv yees ntawm cov ntaub ntawv preclinical thiab txhawb nqa kev txhais lus kho mob zoo dua.

Ib qho zoo -cov tswv yim uas tsis muaj chaw kho mob yog qhov tseem ceeb rau kev txo qis qhov tsis paub tseeb hauv kev tsim tshuaj. Ua tib zoo txiav txim siab txog hom kev xaiv, kev tsim koob tshuaj, qauv qauv, thiab cov txheej txheem tshuaj ntsuam xyuas kom ntseeg tau siab - cov ntaub ntawv zoo uas tuaj yeem ntseeg tau cov kev txiav txim siab kho mob.

Thaum koom ua ke nrog cov txheej txheem kev txhais lus siab, xws li cov muab los ntawm Prisys Biotech, PK cov kev tshawb fawb dhau los ua cov cuab yeej muaj zog txhawm rau txhawm rau txhawm rau txhim kho lub sijhawm thiab txhim kho qhov tshwm sim ntawm kev kho mob ua tiav.

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