of 5

wallace1981 tdm genta.pdf

Description
CLINICAL APPLICATION OF PHARMACOKINETICS IN ADJUSTING GENTAMICIN DOSAGE: CASE REPORTS by Sylvia M. Wallace, Kathy Gesy, and Dennis K. J. Gorecki GENTAMICIN is an aminoglycoside antibiotic whose Both therapeutic and toxic effects of gentamicin are primary therapeutic role is the treatment of infections related to dose and serum levels of the drug. For caused b
Transcript
  CLINICALAPPLICATIONOFPHARMACOKINETICS IN ADJUSTINGGENTAMICINDOSAGE:CASEREPORTS by Sylvia M.Wallace, Kathy Gesy, and Dennis K J. Gorecki GENTAMICIN isanaminoglycosideantibioticwhoseprimarytherapeuticroleisthetreatmentofinfectionscausedbygram-negative Enterobacteriaceae and Pseudomonasaeruginosa. Toensurethattheantibioticwillbeeffective,particularlyinlife-threateninginfections,anadequatedoseofgentamicinmustbeadministered.However,becausegentamicinhasalowtherapeuticindex,thedrugmustbeadministeredwithcautiontoensurethatpatientsdonotreceiveatoxicdose.Toxiceffectsontheauditory-vestibularapparatusandthekidneycanresultinhearingloss,lossofequilibrium,andacuterenaltubularnecrosis.Theincidenceoftoxiceffectscanberelatedtothedosageofdrug,lengthoftreatment,preexistingrenaldysfunction,andageofthepatient. 1 Gentamiciniseliminatedfromthebodyprimarilybyrenalexcretion.Totalbodyclearanceofgentamicinisdirectlyproportionaltocreatinineclearance. Theeliminationhalf-liferangesfromtwotothreehoursinpatientswithnormalrenalfunction, upto69hoursinanuricpatients.' For mostclinicalapplications,thehalf-lifeiscalculatedassuminggentamicinpharmacokineticscanbedescribedbyaone-compartmentmodel.   serumsamplesareobtainedforaprolongedperiod(e.g.,120hours ),thedeclineofserumlevelsisbiphasicandcanbedescribedbyatwo-compartmentpharmacokineticmodel.Theslowerelimination  13) phasehasanaveragehalf-lifeof53hoursinpatientswithnormalrenalfunctionand173hoursinpatientswithacreatinineclearanceoflessthan25 ml/rnin. Gentamicindispositionisalsoaffectedbyanumberofotherphysiologicandpathologicconditions. Becausegentamicinisdistributedlesstoadiposetissuethantoothertissues,therelativevolumeofdistributionislowerinobesesubjectsthaninsubjectswithnormalweight. 6 Predictionofserumlevelsismoreaccuratewhenbasedonestimatesofleanbodyweight(LBW)thanontotalbodyweight(TBW).4Volumesofdistributioninpatientswithascitesappeartobelargerthaninnormalpatients. SYLVIA M WALLACE B.S.P.,Ph.D.,isAssociateProfessor,CollegeofPharmacy; KATHY GESY B.S.P.,isLecturer,CollegeofPharmacy;and DENNIS K J. GORECKI B.S.P.,Ph.D.,isDirector,PharmaceuticalResearchandAnalysisLaboratory,CollegeofPharmacy,UniversityofSaskatchewan,Saskatoon,Saskatchewan,Canada. AddresscorrespondenceandreprintrequeststoDr.S.M.Wallace,CollegeofPharmacy,UniversityofSaskatchewan,Saskatoon,Saskatchewan,CanadaS7N OWO. Boththerapeuticandtoxiceffectsofgentamicinarerelatedtodoseandserumlevelsofthedrug. For treatmentofmostinfections,peakserumlevelsof 5-8 I l g ml areeffective.Slightlyhigherconcentrations(8-10 f.l.g/ml mayberequiredtotreatpneumonias. Highpeakserumlevelsoccurmorefrequentlyinpatientswhodevelopototoxicity.JacksonandArcierireport10of19patientsexhibitingototoxicityashavinggentamicinserumlevelsgreaterthan8 f.l.g/ml withsevenofthetenhavinglevelsbetween16and 40 I l g ml, 9 Patientswithtroughlevelshigherthan2 I l g mlexhibitahigherincidenceofnephrotoxicity. 10 Tominimizetoxicity,dosageregimensshouldbedesignedtoavoidexcessiveserumlevelsofgentamicin,(thatis,peaklevelsgreaterthan10-12 f.l.g/ml andtroughlevelsabove2-3 f.l.g/ m l 8 Becauseofalowtherapeuticindexandvariabilityingentamicindisposition,dosageshouldbeindividuallyadjustedforeachpatient.Sinceeliminationofgentamicinisprimarilydependentonrenalfunction,mostmethodsofadjustingdosagesforpatientsrelyonanestimateofkidneyfunction(e.g.,serumcreatinine,creatinineclearance).4  11   serumlevelsofgentamicinaremeasured,moreprecisedefinitionofpharmacokineticparametersandadjustmentofdosagearepossible. Sincethedosagerequiredtomaintaintherapeuticbutnontoxicdruglevelsisdifferentforeachpatient,thecorrectbalancecanbestbeachievedbyajudiciouschoiceoftheinitialregimen(determinedwithreferencetokidneyfunction),measurementofdruglevels,andsubsequentadjustmentofdosage.Inourexperience,methodsforpredictinggentamicinlevelsanddesigningoptimaldosageschedulesaremostsuccessfulinpatientswithaverageweight,goodrenalfunction,andrelativelystableclinicalcondition.Despitetheaccumulationofpharmacokineticinformationrelatingtotheaminoglycosideantibiotics,pharmacokineticpredictionsalonecannotanticipatethephysiologicandpathologicchangesthatoccurinmanyhospitalizedpatientswithacuteillnesses.Thefollowingcasehistorieswereselectedtoillustratetheuseofpharmacokineticmonitoringofpatients,andtoemphasizethenecessityofclinicalassessmenttomodifyrecommendationsbasedonpharmacokineticanalysis.AllcasehistoriesreportedareforinpatientsatSaskatoonCityHospital(Saskatoon,Saskatchewan).Allserumsampleswereanalyzedinduplicatebyradioimmunoassay(NewEnglandNuclearcommercialkit,Rianenw)atthePharmaceuticalResearchand Drug IntelligenceandClinicalPharmacy V 15 SEPT81 651  at UNIV OF LETHBRIDGE on June 9, 2016aop.sagepub.comDownloaded from   AnalysisLaboratoryoftheCollegeofPharmacy,UniversityofSaskatchewan.Gentamicinwasadministeredbyintravenousinfusionforaperiodof¥2toIhourasorderedbythephysician.Theexacttimeofstartingandstoppingtheinfusionwasnotedbythenursingstaff.Bloodsamplesformeasurementofgentamicinlevelswereusuallydrawnwhenthepatientwasatsteadystate,immediatelypriortoadose,and30minutespostinfusion.Theexacttimeofbloodcollectionwasnotedbythephlebotomist.Serumwasseparatedfrombloodandanalyzedforgentamicinbyradioimmunoassay.Theserumgentamicinlevelswereplottedonsemi-logarithmicgraphpaper(logarithmofconcentrationagainsttime).Theserumlevelmeasuredbeforethedosewasassumedtoalsorepresentthelevelwhichwouldbeachievedattheendofthefollowingdosinginterval(sincethepatientwasatsteadystate).Theeliminationhalf-life  t¥2) wasestimatedfromthegraph.Thepeakconcentration(Cmax)wasestimatedbyextrapolatingthegraphtothetimetheinfusionhadterminated.Thevolumeofdistribution(Vd)wasestimatedfromthemeasuredgentamicinlevelsusingthefollowingequation: 12 _k,  1 e-kdt') V d- -k kd(Cmax-Cmined   Eq.Iwhere k, =infusionrate(mggentamicin/h);kd=eliminationrateconstant  0.693/t¥2); t'=lengthoftheinfusion  h); Cmax=peakgentamicinconcentration,thatis,attheendoftheinfusion(ug/rnl};andCmn=troughgentamicinconcentrationattheendofthepreviousdosinginterval(}-lg/ml).ThedosagerequiredtoachieveatherapeuticpeakandtroughlevelatsteadystatewascalculatedfromEquation2,whereT=dosageinterval:k= Cmnxk dVd  I -e-kdT) o  1 e-kdt')Eq.2Thisdosagewasroundedtothenearesteasilyadministereddoseandthepeakandtroughthatwouldbeachievedatthisinfusionratecalculatedas: Eq.3 Eq.4 Leanbodyweight(LBW)wasestimatedas: 13 LBW(Males)=50kg   2.3kg/inchofheightover5ft.LBW(Females) =45.5 kg   2.3kg/inchofheightover5ft.  SE REPORTS CASE1A56-year-oldfemale(weight48kg,height5')wasadmittedMay30withaone-monthhistoryofchills,weightloss,andgeneralmalaise.Onadmission,thepatientwasfebrile(T38.2°C);laboratorytestswere: 652 whitebloodcount(WBC) 15900 withleftshift,hemoglobin(Hb)10.6 g/100 ml,hematocrit(Hct)31.5 ,sodium137 mEq/L, potassium·4.6 mEq/L, chloride102.5 mEq/L, bloodureanitrogen(BUN)8mg/lOOml,serumcreatinine1.2mg/lOOml.Bloodandurineculturesshowednobacterialgrowth.Vaginalculturesshowedgrowthof  nterob cterclo c e sensitivetogentamicin.Thepreliminarydiagnosiswaspelvicperitonitiswithpossibleabscess.Gentamicintherapy(80mgivq8h)andampicillin1givq6hwereinitiatedat2200hMay30.SerumgentamicinlevelsweredeterminedJune2beforeandafteradministrationoftheninthdose.Apeaklevelof11.4.ug/mlandatroughlevelof2.5.ug/mlwereachieved.Adecreaseindoseto50mgivq8hwasrecommended.Fortyhoursafterdecreasingthedose,serumgentamicinlevelswere7.9 ~ g ml forthepeakand2.2.ug/mlforthetrough.Clindamycin300mgq6hwasstartedJune4.OnJune5,examinationbyultrasoundrevealedapelvicmass.AlaparotomywasperformedJune10.Afixed,poorlydifferentiatedcarcinomaofthepelviswasdiagnosedandremoved.AntibioticswerediscontinuedJune13.ThepatientwasdischargedingoodconditionJune20. Thispatienthadgoodrenalfunction,averagebodyweight,andremainedrelativelystablethroughouttheperiodofhospitalization.Herserumcreatinineremainedbetween1.0and1.2mg/IOOml.Thedosageinitiallyprescribedwastoohighandnecessitatedareduction.Theschedulerecommended(50mg q8h), basedonestimationofthepatient's Ve (7.9L)andt¥2(3.7h)fromthegentamicinlevelsmeasured,waspredictedtoachieveapeakserumlevelof7.4 } lg/ml andatroughlevelof2.2 } lg/ml Thepeaklevelachievedwas7.9 } lg/ml andthetrough,2.2 } lg/ml CASE2A74-year-oldmale(weight90kg,height5'6 )wasadmittedtotheIntensiveCareUnit(lCU)June3withsignsofintestinalobstruction.Onexamination,thepatientexhibitedcyanosisandadistendedabdomen.Hewasvomiting,sweating,andhadclammyskin.Hispulsewasweakandbloodpressurewasnotrecordable.Thepreliminarydiagnosiswasperitonitissecondarytoobstructionandperforationofthesmallbowel.Ampicillin1givq6hwasorderedonadmission.Laboratorydataonadmissionwere:WBC11100,Hb19.1 g/100 ml,Hct 54 , sodium142 mEq/L, potassium4 mEq/L, chloride92.5 mEq/L, BUN64 mg 1 ml,serumcreatinine3.4 mg l ml.Thepatienthadnohistoryofrenaldisease.SurgerywasperformedJune3,andasmallsegmentofhissmallbowelwasresected.Thepatientwasdigitalized(lanatosideC0.4mgiv)andcurarized(pancuroniumbromide)duringsurgeryandwasmaintainedonarespiratoraftersurgery.Dopaminewasadministeredbyanintravenousinfusionwiththerateofadministrationadjustedtomaintainasystolicbloodpressureof90mmHg.Intravenousfluidsandalbuminwereadministeredtomaintaincentralvenouspressure.Gentamicin80mgivwasadministered  l hduration)beforesurgeryat2030hJune3.Becauseofhishighserumcreatinineand poor renalfunction,serumsampleswereanalyzedbeforeadministeringthenextdoseofgentamicin.Gentamicinlevelswere1.85 I g/ml at0800 hand 1.15.ug/mlat1400honJune4.Elimination t\ 2 andV d estimatedfromthesemeasurementswere9 hand 18L(28percentLBW),respec-  at UNIV OF LETHBRIDGE on June 9, 2016aop.sagepub.comDownloaded from   tively.Basedonthesepharmacokineticparameters,adoseof100mgq24hwasrecommended.Gentamicin100mgwasadministeredat1800h June 4and5. The patientdevelopedan erythematous rash June 4.Ampicillinwasdiscontinued June 5,andtwodosesofchlorpheniramine10mgivq12hwereadministered. Serum gentamicinlevelswererepeated June 6at0800h(3.6.ug/ml)and1330h(2.6.ug/ml). The t l  had increasedto12 h n V<\ decreasedslightlyto16L. Serum creatinine during thisperiodrosefrom3.4to3.5mg/lOOmI. The scheduleof100mgq24hwasmaintained June 6through8.By June 8,thepatient'sconditionwasstableandgraduallyimproving.His abdomen wasmoderatelydistendedwithindicationsofsomefluidaccumulation.Infact,he had accumulatedapositivefluidbalanceofapproximately4L. Serum creatininedecreasedto2.4mg/lOOml June 7, and thento1.4 mg/100 ml June 8. Serum gentamicinlevelsmeasuredJune9were1.5.ug/mlat0810 hand 1.05.ug/mlat1315h.Basedonthesemeasurements,the t'l2 had decreasedslightlyto10handtheV   increasedsignificantlyto32L(50percentLBW). The extrapolatedvalueforthe peakserum levelwas5.ug/mI. The gentamicindosagewasthenincreasedto120mgq24h. The patientcontinuedtoimprove,andthedopaminewasdiscontinued June 10.Hisdailyfluidbalance became negative.OnJune11, serum levelsofgentamicinmeasuredat0830 hand 1300hwere1.4.ug/ml and 0.6.ug/ml,respectively.Reflectingthe improvement inrenalfunction,the tlh forgentamicin had decreasedsignificantlyto3.7h(serumcreatinineon June 10was1.2mg/lOOml),Withthedisappearanceofperitonealfluidaccumulation,theV   hadreturned to normal (16L,25percentLBW).Withthedecreasein t l2 achangeinthedosagescheduleto90rngq12hwasrecommended.ByJune16,hiswoundwashealing,andhehadbeenextubated,nolongerrequiringtherespirator. The gentamicinwasdiscontinued. The patientreturnedtothewardJune17andwasdischarged June 24. Withrapidlychangingrenalfunction,significantchangesingentamicindispositionwereanticipated.Changesingentamicinhalf-lifedidnotcoincidewiththechangesinserumcreatinine.Thehalf-liferemainedprolongedforseveraldaysaftertheserumcreatininebegantodecrease.Coupledwiththechangesinrenalfunction,the V \ changeddramaticallyduringthecourseofthepatient'shospitalstay.Peritonealfluidaccumulationproducedmarkeddistensionofhisabdomen.The V \ increasedto50percentLBWandthenreturnedtonormal(25percentLBW)whenthefluidhaddissipated.AlthoughtheV d inmostpatientsisestimatedas20-25percentLBW, V \ valuesof31-84percentLBWhavebeenreportedforpatientswithascites.'Inapatientwithanabnormallylarge V pharmacokineticpredictionsmustbetemperedbyclinicaljudgment.AnticipatingthatthefluidaccumulationandV d increase(from16to32 L) weretransient,thegentamicindosagewasnotdoubledbutwasonlyincreasedfrom100to120mgq24h.Asthepatient'sconditionstabilizedwithanormal V decreasedserumcreatinine,anddecreasedgentamicinhalf-life,thedosingintervalwasdecreasedfrom24to12hourstomaintaintherapeuticlevelsforlongerperiods.Thedosageschedulerequiredtomaintaintherapeuticlevelsofgentamicininthispatientwasvariable. GENT MI IN DOS GE Bothhalf-lifeand V \ changedsignificantly. For suchpatients,serumgentamicinlevelsshouldbemeasuredfrequentlyandgentamicindosageadjustedaccordingly.Laboratorytestsaswellastheclinicalstatusofthepatientshouldalertthepharmacistorphysicianandhelptoidentifypatientsrequiringfrequentserumlevelmonitoring.Inthiscase,decreasingserumcreatinineindicatedagradualimprovementinrenalfunctionwhilemarkedabdominaldistensionindicatedasignificantaccumulationofperitonealfluid. CASE 3A56-year-oldmale(weight90kg,height5'10 )wasadmitted May 17withfever,chills,sweating,andleftsubcostalpleuriticpain. During theprevioustwoweeks,thepatienthadcomplainedofincreasedshortnessofbreath,decreasedenergy, and frontalheadaches.He had experienced recurrent respiratoryinfectionsforthepastsixmonths. The patientwasreferredwithapreliminarydiagnosisofacuteleukemia.Onadmissionhisvitalsignswere:P88andregular,BP 120/80 mmHg,andT sti-c. AchestX-rayshowedsignsofleftlowerlobeconsolidation.Labora tory testsonadmissionwere:WBC33100(with1 neutrophils,18 lymphocytes, 27 monocytes,and 35 blastcells),Hb10.3g/lOOml, Hct 31.2 , platelets 152000, sodium142 mEq/L, potassium4.2 mEq/L, chloride105 mEq/L, BUN 18mg/IOOml, andserum creatinine1.1 mg/l00 ml,Cephalothin1givq6handgentamicin100mgivwereadministeredat1230hMay18followedbygentamicin80mgq8hbeginningat2200h. Serum gentamicinlevelswereanalyzed May 20beforeand after administrationoftheeighthdose. The peaklevelwas3.75.ug/mlandthetrough,0.9.ug/mI.OnMay22,thedosewasincreasedto120mgq8hat1400h. Laboratory reportsconfirmedadiagnosisofacutemyelomonocyticleukemiawithpossibleleftlowerlobeinfiltration. Chemotherapy (adriamycin30mgivfor3dandcytosinearabinoside150mgfor5d)wasscheduledforMay21.Metoclopramide(10mgivbeforeadriamycin and cytosinearabinoside)andchlorpromazine(25rngimprn)were ordered tocontrolnausea.Gentamicinlevelsweremeasured May 27.Withadoseof120mgq8h,apeakof10.3.ug/mlandatroughof2.ug/mlwereachieved.AchestX-rayshowedclearingofleftlungconsolidation;theantibioticswerediscontinued May 29. Two days after discontinuingthegentamicintherapy,thepatientdevelopedadentalabscessandgentamicintherapywasreinstitutedataloadingdoseof120mgfollowedby100mgivq8h. The peaklevelonthisregimenwas6.8.ug/ml and thetrough,1.8.ug/mI. Initialestimatesofpharmacokineticparametersbasedonapeaklevelof3.75f.lg/mlandatroughlevelof0.9f.lg/mlforadosingscheduleof80mgq8hwere3.6hforthehalf-lifeand26L  37 percent LBW) for V \ The V \ islargeandperhapsdue,inpart,toaccumulationoffluid.ThedailyfluidbalanceremainedpositiveuntilMay23.PharmacokineticparametersdeterminedMay27,ninedaysafterstartingthegentamicinandfivedaysafterincreasingthedosage,reflectedachangeinthepatient'sclinicalcondition.Althoughthehalf-liferemainedessentiallyunchanged(3.4 h), the v, decreasedto12.5L  17 percent LBW). FromMay21-25thepatientreceived DrugIntelligenceandClinicalPharmacy VOL 15 SEPT81 653  at UNIV OF LETHBRIDGE on June 9, 2016aop.sagepub.comDownloaded from   chemotherapyduringwhichtimeheexperiencednausea and vomitinganddidnot eat regularly.Betweenadmission  May17)and May24,thepatientlost3kgofbodyweight.Hisrenalfunction,asmonitoredbyserumcreatinine,remainedunchanged(1.1 mg/ 100 ml). The decreasingV d couldbeattributedtoclearingofthepleuralexudateaswellastofluid and weightlossduringchemotherapy.Whengentamicinwasreinstituted June 2,thehalfliferemainedapproximatelythesame  3.7 h). The Ve increasedto17.7L  24 percent LBW), avaluewithinthenormalrange. The patientwasonceagaineatingwell;nausea and vomitingduetothechemotherapy had ceased.Althoughthepatient'shalf-liferemainedrelativelyconstantthroughoutthecourseofgentamicintherapy,the Ve changedsignificantly. The changesin Ve reflectedchangesinthepatient'sclinicalcondition,thatis,fromabnormalfluidaccumulationtodehydrationsecondarytoprolongednauseaandvomiting.Anydosingrecommendationsbasedonpharmacokineticpredictionsmustbeinfluencedbytheclinicalchangesnoted.Withpriorknowledgethatthepatientistoreceiveachemotherapyregimen,whichoftenproducesnauseaandvomiting,contractionofthe V \ forgentamicinshouldbeanticipated.Anyadjustmentsindosageshouldbeconservative.Thus,althoughinitialestimatesofpharmacokineticparametersinthiscasesuggestadoublingofthedose(from80to160 q8h), thedosageincreaserecommendedshouldbeconservative  from 80to 120 mg q8h). Inaddition,serumlevelsshouldbemonitoredmorefrequentlyduringchemotherapysincetheexactchangein   d cannotbepredicted. CASE4A3I-year-oldmale(weight43.2kg,height5'4 )withadvancedmusculardystrophywasadmittedtothe ICU April30withrespiratoryfailure,acutebronchitis,increasingdyspnea,andretentionofbronchialsecretions.Thepatienthadseverepulmonaryrestrictionbecauseofskeletaldeformityandmusculoskeletalweakness.Ampicillin500rngivq6hwasadministeredApril30.AtracheostomywasperformedMay3.ByMay7,thepatienthaddevelopedbilateralpleuraleffusionsinbothlungbasesandhadaccumulatedafluidbalanceof7L.Furosemide(upto40mgq6h)wasadministered.SputumculturesofMay7reportedgrowthof  lebsiellapneumoniae and  seudomonasmaltophilia resistanttotheaminoglycosidesandampicillin;sensitivetocarbenicillin,sulfonamides,andco-trimoxazole.Sulfisoxazole0.5gqidwasadministered.OnMay21,thepatientwasstillfebrile(39°C)andhaddevelopedanerythematousrash.Ampicillinwasdiscontinued,andcephalexin500mgqidwasstarted.OnMay30,sputumculturesshowedlightgrowthof  seudomonasaeru- ginosa (sensitivetocephalosporinsandgentamicin).AchestX-rayshowedevidenceofrightlowerlobepneumonia.Cephalexinandsulfisoxazolewerediscontinued.Cephalothin500mgivq6handgentamicin80mgivq8hwereinitiatedat1700honMay30.LaboratorytestsofMay23were:WBC10300,Hb14.9g/IOOml,Hct 47.4 , sodium137 mEq/L, potassium3.4 mEq/L, chloride82 mEq/L, BUN II mg/100 ml,andserumcreatinine0.3mg/100mI.SerumlevelsofgentamicinonJune2wereatroughof3.4J.tg/mlandapeakof II J.tg/mI.Basedonphar- 654 macokineticparameters,adecreaseindoseto70mgq12hwasrecommended.Levelsmeasuredafterdosereductionwere8J.tg/mlforthepeakand1.2J.tg/mlforthetrough. Inpatientswithmusculardystrophy,serumcreatininecannotbeusedasameasureofrenalfunctiontoaidintheadjustmentofdosageoftheaminoglycosideantibiotics.Asinthispatient,serumcreatinineislowbecauseofadecreasedrateofcreatinineproduction.Serumconcentrationsofcreatineandcreatinephosphokinaseare elevated.l Other testsofrenalfunctionsuchasinulinandp-arninohippurateclearancegivenormalvalues. The half-life,asestimatedfrommeasuredgentamicinlevels,was4h and theV d, 9L(21percent LBW) .Asaresult,adosingintervallongerthaneighthourswasrequiredtomaintainatroughlevelbelow that associatedwithtoxicity  2 flg/ml), but apeaklevelhighenoughfortreatmentofpneumonia(8 flg/ml).The primaryaiminalteringthedosageschedulefrom80mgq8hto70mg q12h wasto de creasethetroughlevelof3.4flg/ml. Thepeak andtroughvaluespredictedusingEquations3and4,a   of4h, V \ of   L, and adosagescheduleof70mgq12hwere8.2 ltg mland 1. 3  lg ml, Pharmacokineticmodelsofgentamicindosingcannotbeappliedinisolation.Clinicalassessmentoftheindividualpatientisofmajorimportance and will,inmanycases,determinetheoutcomeofdosagerecommendations. The precedingcases,encounteredin our pharmacokineticpractice,aremeanttoserveasexamplesofhowpracticalapplicationofpharmacokineticsmustbetemperedwithclinicaljudgment.e- Wewishtothankthepharmacists,physicians,laboratorytechnologists,andnursesofSaskatoonCityHospitalfortheircooperationandassistanceinconductingthe pharma- cokineticservice. KEY WOR S pharmacokinetics,gentamicin,serumconcentrations,aminoglycosideantibiotics. EXTR CTO Losmodelosfarmacocineticos para dosificargentamicinanopuedenaplicarseaisladamente.Loscambiosfisiologicosypatologicosqueocurrenenmuchospacienteshospitalizadoscuyoestadoclinicoesinestablenopuedenseranticipadosporprediccionesfarrnacocineticasunicarnente.Sepresentancuatrocasos para ilustrarelusodevigilanciafarmacocineticaenpacientesy para enfatizarlanecesidaddeutilizarlaevaluacionclinicadelpaciente para modificaraquellasrecomendacionesbasadasenanalisisfarmacocinetico, Luz M. GUTIERREZ RESUME Lefaibleindextherapeutlquedelagentamicine,antibiotiquedelac1assedesaminoglycosides,estbiendocumente,Despiesseriquessuperieurs a 8-10J.tg/ml ont eteassocies a uneincidenceeleveed'ototoxicite;demerne,des creux superieurs a 2-3J.tg/mlont-ilseteincriminesdansl'etiologiedereactionsnephrotoxiques a cetantibiotique.Malgrel'abondantedocumentationconsacree a cetagentchirniotherapeutique,ildemeureencoredifficile a l'heureactuelled'instaurer  at UNIV OF LETHBRIDGE on June 9, 2016aop.sagepub.comDownloaded from 
We Need Your Support
Thank you for visiting our website and your interest in our free products and services. We are nonprofit website to share and download documents. To the running of this website, we need your help to support us.

Thanks to everyone for your continued support.

No, Thanks