PK Statistics: Tsis yog -Compartmental Analysis (NCA) Parameters Thiab Preclinical Applications

Nyob rau hauv preclinical kev tshawb fawb theem ntawm txoj kev loj hlob tshuaj, qhov tseeb txhais ntawmPharmacokinetic (PK)cov ntaub ntawv yog qhov tseem ceeb.Tsis yog -Compartmental Analysis (NCA), raws li ib tug classic statistical txoj kev nyob rau hauv pharmacokinetics, tau dhau los ua tus nyiam cov cuab yeej rau regulatory xa (IND) thiab kev kawm ntawv cov ntaub ntawv vim nws muaj kev ywj pheej los ntawm ib tug tshwj xeeb compartment assumpions.

Cov txheej txheem ntawm cov tshuaj nyob rau hauv lub cev yog feem ntau summarized liADME(Kev nqus, faib, metabolism, thiab excretion). Txhawm rau txheeb xyuas cov txheej txheem no, cov kws tshawb fawb vam khom cov qauv lej. Piv nrog rau cov qauv kev sib xyaw ua ke,Tsis yog -Compartmental Analysis (NCA)siv txoj kev ua lej xws li txoj cai trapezoidal los xam cov tsis ncaj qha los ntawm cov tshuaj concentration- cov ntaub ntawv sijhawm.

Vim tias nws xav tau cov kev xav tsawg dua thiab muab cov txiaj ntsig zoo, rov tsim dua tshiab, NCA tau siv dav hauv cov kev tshawb fawb txog kev kho mob preclinical thiab chaw kho mob rau ntau yam kev kho mob, los ntawmme me moleculesrauloj molecule biologics.

Cov tsis suav ntawm NCA tuaj yeem muab faib ua peb pawg tseem ceeb: tsis muaj kev cuam tshuam txog tshuajnphav, parameter reflectingcov yam ntxwv ntawm lub sijhawm, thiab parameter reflectingclearance thiab faibkhoom.

Cov kev txwv no ncaj qha cuam tshuam txog qib concentration ntawm cov tshuaj hauv lub cev thiab yog cov cim tseem ceeb rau kev ntsuas kev ua tau zoo thiab kev nyab xeeb.

Cmax (Peak Concentration):

Txhais: Qhov siab tshaj plaws pom cov ntshav / ntshav siab tom qab noj.

Qhov tseem ceeb: Zoo sib xws rau qhov siv ntawm cov tshuaj cov nyhuv thiab muaj peev xwm toxicity. Hauv ntau yam -dosing scenarios, nws sawv cev rau qhov siab tshaj plaws nyob rau hauv ib lub sijhawm noj.

Cmin thiab Ctrough:

Cmin: Qhov tsawg kawg nkaus concentration pomhauvlub sij hawm dosing.

Ctrough: Qhov concentration tam sim ua ntej koob tshuaj tom ntej ntawm lub xeev khov kho (kawg ntawm lub sijhawm noj tshuaj).

Nco tseg: Nyob ruaj khov, yog tias qhov ua ntej - koob tshuaj concentration yog qhov qis tshaj plaws, cov lej ntawm Cmin thiab Ctrough tej zaum yuav zoo ib yam, tab sis lawv cov ntsiab lus txawv (saib cov lus hauv qab no).

Daim duab: Steady-lub xeev cov tshuaj concentration- lub sij hawm nkhaus, qhia kev sib raug zoo ntawm qhov sib txawv ntawm qhov sib txawv thiab Yam tsawg kawg nkaus Kev Cuam Tshuam - MEC

Cavg (Average Concentration):

Txhais: Qhov nruab nrab concentration thaum lub sij hawm noj tshuaj ntawm lub xeev khov kho (Formula: AUCtau / τ).

Qhov tseem ceeb: Rau cov tshuaj uas qhov ua tau zoo yog proportional rau tag nrho cov raug (xws li, tej yam tshuaj tua kab mob los yog oncology tshuaj), Cavg yog ib tug tseem ceeb cov ntaub ntawv qhia.

AUC (Area Under the Curve):

AUClast: Lub cheeb tsam nyob rau hauv qhov nkhaus ntawm lub sij hawm xoom mus rau lub sij hawm quantifiable kawg.

AUCinf: Lub cheeb tsam nyob rau hauv lub nkhaus extrapolated ntawm lub sij hawm xoom mus rau infinity.

Kev Tswj Xyuas Zoo: Qhov ratio ntawmAUClast / AUCinf yuav tsum siab dua lossis sib npaug li 80%. Qhov no ua kom ntseeg tau tias lub sijhawm ua piv txwv txaus los npog cov tshuaj thawj theem tshem tawm.

AUCtau: Lub cheeb tsam nyob rau hauv lub nkhaus nyob rau hauv ib tug dosing lub sij hawm nyob rau hauv khov kho.

Daim duab: xam thiab extrapolation ntawm AUC-Qhov chaw ntxoov ntxoo sawv cev rau AUClast, thaum daim duab peb sab nyob rau hauv kab dashed sawv cev rau feem extrapolated

Tmax: Lub sijhawm uas Cmax tau pom. Rau tam sim no - tso tawm formulations, qhov no qhia txog tus nqi nqus; rau kev txhawb nqa -tso tawm formulations, nws qhia txog kev tso tawm yam ntxwv.

Tag (Lag Time): Lub sij hawm ncua ntawm kev tswj hwm tshuaj thiab thawj qhov ntsuas tau. Nws feem ntau yog siv los ntsuas qhov kev ncua qeeb ntawm enteric-coated formulations.

T1/2 (Terminal Elimination Ib nrab-lub neej):

Txhais: Lub sij hawm yuav tsum tau rau cov tshuaj concentration kom txo tau ib nrab thaum lub sij hawm tshem tawm theem (Formula: ln2 / λz).

Qhov tseem ceeb: Txiav txim seb qhov ntau npaum li cas thiab lub sij hawm yuav tsum tau mus txog lub xeev khov kho (feem ntau yog 5–7 ib nrab-lub neej).

λz (Lambda z, Terminal tshem tawm tus nqi tas li):

Tau txais los ntawm qhov tsis zoo nqes hav ntawm cov kab rov ua dua ntawm cov cav- hloov pauv lub davhlau ya nyob twg concentration- cov ntaub ntawv sijhawm. Nws yog lub hauv paus rau kev xam T1/2 thiab AUCinf.

Daim duab: Linear regression haum siv cov ntsiab lus davhlau ya nyob twg los xam λz

CL (Kev tshem tawm):

Lub ntim ntawm plasma los ntawm cov tshuaj raug tshem tawm tag nrho ib chav tsev ntawm lub sijhawm.

Intravenous (IV): CL=Dose / AUCinf

Extravascular (piv txwv li, PO, SC): CL/F=Dose / AUCinf (qhov twg F yog Bioavailability). Txij li F feem ntau tsis paub, qhov no suav covPom meej Clearance.

Vz (Vume of Distribution):

Ib qho theoretical ntim qhia txog qhov kev faib tshuaj hauv lub cev.

Kev suav: Vz=CL / λz.

Qhov tseem ceeb: Ib tug loj Vz qhia tau hais tias cov tshuaj yog feem ntau faib nyob rau hauv cov ntaub so ntswg; ib tug me me Vz (ze rau plasma ntim) qhia tias cov tshuaj yog nyob rau hauv feem ntau ntawm cov ntshav.

4. Tshwj xeeb Parameters rau ntau yam koob tshuaj

DF (Kev hloov pauv): xam raws li (Cmax - Ctrough) / Cavg. Qhov no qhia txog qhov amplitude ntawm qhov sib txawv ntawm qhov concentration ntawm lub xeev khov kho; Cov kev hloov pauv me me feem ntau cuam tshuam nrog kev ruaj ntseg profile zoo dua.

Rac (Accumulation Ratio): Tus piv ntawm khov kho - xeev AUC rau ib zaug - koob AUC. Yog tias Rac> 1, nws qhia tias muaj cov tshuaj tsub zuj zuj hauv lub cev, qhia tias yuav tsum tau kho cov tshuaj noj.

Qhov tseeb PK parameter xam yog nyob ntawm siab -cov ntaub ntawv nyoos zoo. Hauv NCA, tus tsim ntawmsampling lub sij hawm cov ntsiab lus, covprecision ntawm sampling kev ua haujlwm, thiab covstandardization ntawm cov qauv uancaj qha txiav txim siab qhov kev cia siab ntawm Cmax, Tmax, thiab lub davhlau ya nyob twg theem haum.

Lub Prisys Biotech Advantage

Raws li kev kho mob preclinical CRO tshwj xeeb hauvTsis yog -Human Primate (NHP)thiab lwm cov qauv tsiaj loj, Prisys Biotech muaj qhov tshwj xeeb zoo hauv PK / PD kev tshawb fawb:

• Siab -Txoj kev sim Platform: Peb qhov chaw muaj tag nrhoAAALAC tau lees paub, ua kom muaj kev noj qab haus huv tsiaj thiab kev lees paub thoob ntiaj teb ntawm cov ntaub ntawv sim.
• Precision Operations Team: Peb pab neeg ua haujlwm paub txog tuaj yeem ua tiav txoj kev tswj hwm txoj hauv kev (piv txwv li, Intracerebral, Intravitreal, Intrathecal txhaj) thiab siab -ntau zaus ua piv txwv, kom ntseeg tau qhov tseeb ntawm Tmax.
• Kev txhais lus tshuaj Perspective: Leveraging ib lub tsev qiv ntawv nplua nuj ntawmkab mob qauv(piv txwv li, kab mob siab metabolism, kab mob plawv, thiab CNS), peb muab kev txhais lus tshawb fawb ntawm PK cov yam ntxwv hauv cov kab mob pathological, ua kom muaj kev txhais lus tsis sib haum xeeb los ntawm Pre- kho mob mus rau theem kho mob.

Xaus

Prisys Biotechtau cog lus los ua tus thawj coj hauv tsiaj tsiaj loj thiab kev tshawb fawb txog kev ua tau zoo. Yog tias koj xav tau qib siab -PK / PD cov kev pabcuam tshawb fawb, kev txhim kho tus qauv kab mob, lossis kev pabcuam kev ntsuas kev nyab xeeb, thov hu rau peb.

Tiv tauj peb

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