Andersons pediatric cardiology 2105
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Terms
Integraltothisdiscussionisareviewofthebasicterminologyutilizedinclinical
pharmacology.Thefollowingtermsaredescribedingreaterdetailinreferenced
texts.5,6
Absorptionistheprocessofdrugmovementfromthesiteofadministration
orapplicationintosystemiccirculation.Therate(e.g.,timetomaximal
concentration;tmax)andextent(e.g.,bioavailability)ofabsorptioncan
beimpactedbydrugfactors(e.g.,formulation,solubility,protein
binding,lipid/water-partitioncoefficient)and/orpatientfactors(e.g.,
proteinbindingcapacity,gastricemptyingtime,portalvenousstasis).
Areaunderthecurve(AUC)istheareaundertheplasmadrug
concentration–timecurve.Inthedomainofpharmacokinetics,AUCand
maximalplasmadrugconcentration(Cmax)representtheimportant
parametersbywhichonecanquantitatehowmuchsystemicexposure
(e.g.,dose-exposurerelationship)occursoveragivenperiodoftime(Fig.
79.1).Timetomaximalplasmadrugconcentration(Tmax)representsthe
timerequiredfordrugabsorptionafterextravascularadministration.
Plasmaconcentrationvs.timecurve.Thisexampleofa
pharmacokineticprofilewasacquiredover12hours.Eachblack
dotrepresentsthetimepointatwhichaplasmasamplewas
obtained.Theareaundertheplasmaconcentrationcurve(AUC)
FIG.79.1
istheamountofdrugexposurethatoccursoveragiventime
period.Thisexampledemonstratesthedrugexposureover12
hours,althoughthisvaluecanbeextrapolatedtoinfinity.The
maximalplasmadrugconcentration(Cmax)andtimetomaximal
plasmadrugconcentration(Tmax)aredemonstratedhere.
Bioavailabilityisthefractionofadrug,administeredbyarouteotherthan
intravenous,thatreachesthesystemiccirculation.Theaforementioned
drugandpatientfactorsinfluencethedegreeofsystemicexposurethat
occursafteragivendose(e.g.,dose-exposurerelationship).
Clearanceisthepharmacokineticmeasurementofthevolumeofplasma
fromwhichasubstanceiscompletelyremovedperunittime.
Dispositionreferstotheentireprocessofabsorption,distribution,
metabolism,andelimination(ADME)thatinfluencesthe
pharmacokineticsofadrug.
Distributionisapharmacokinetictermthatdescribesthereversibletransfer
ofadrugfromonelocationtoanotherwithinthebody.
Metabolismisthebiotransformationprocessbyphase1and/or2
metabolizingenzymestoenhancetheexcretionofdrugs.Ofnote,
metabolismmaycontributetotheinactivation(e.g.,verapamil)or
activation(e.g.,enalaprilat)ofadrugmoiety.Phase1iscomposedof
oxidation,reduction,hydrolysis,andmethylationreactionsthat
collectivelyservetoincreasethepolarityofadrug.Phase1metabolism
isperformedprimarilybyagroupofoxidasesreferredtoascytochrome
p450enzymes(CYPs).Conversely,phase2metabolismisresponsible
forconvertingdrugsintoamorewater-solubleformforexcretion.
SeveralmajorgenefamiliesthatareinvolvedinphaseIIreactionshave
beenidentified,includingN-acetyltransferases(NAT),uridine
diphosphate–glucuronosyltransferases(UGT),glutathioneS-transferases
(GST),andsulfotransferases(SULT).AnalogoustotheCYP450
families,thesegenefamiliesalsohaveindividualisoforms,eachwithits
ownontogenicprofile.
Pharmacodynamicsentailsboththequalitativeandquantitativedescription
ofdrugeffect.Simplyput,thisiswhatadrugand/ormetabolitedoesto
thebody.
Pharmacokineticsdescribesthechangeofdrugconcentrationinthedrug
productandchangesinconcentrationofadrugand/oritsmetabolitein
thehumanbodyfollowingadministration.Thistermrepresentsthedose-
exposurerelationshipofdrugadministration.Simplyput,thisiswhatthe
bodydoestoadrugand/ormetabolite.
PharmacogeneticsdescribesinterindividualvariationinDNAsequence
relatedtodrugabsorptionanddistribution(PK)ordrugaction(PD).
Pharmacogenomicsistheapplicationofgenomicprinciplesand
technologiesindrugdiscoverytopharmacologicfunction,disposition,
andtherapeuticresponse.
