1Therapeutic Drug Monitoring ofAminoglycosidesJohn C. Rotschafer, Pharm. D.ProfessorCollege of PharmacyUniversity of MinnesotaObjectivesJohn C. Rotschafer, Pharm. D.w Participants will be able to develop a therapeutic drug monitoring planfor aminoglycosides with or without serum concentration time data.w Participants will be able to make appropriate decisions as to the need fortherapeutic drug monitoringw Participants will be able to identify situations appropriate for series orpeak/trough pharmacokinetic monitoring.w Participants will be able to identify an appropriated schedule and timefor aminoglycoside therapy.w Participants will be able to identify appropriate peak and troughconcentrations for conventional and single daily dosing strategies.w Participants will be able to develop a plan to monitor the patient forsuccessful resolution of infection or the development of adverse drugreactions to the aminoglycoside.TDMw Knowing what to do and getting it done ina hospital 24/7 are not one of the samew Part of the art is knowing when to believeand when not to believew Need to be able to function without data,with data, or when data seems to be inquestionw Always need a short term and long termplan2Aminoglycoside Patient CareDecisionsw Decide whether the following are appropriate:n Use alone or in combination with another antibioticn Dose and Intervaln Need for therapeutic serum concentration drugmonitoringl Will aminoglycoside levels be needed?l What type of study if any is neededl How many and when should levels be obtainedn How should patient be monitoredn Duration of therapyInitial Evaluation of AminoglycosideDose & Intervalw Aminoglycoside serum concentration timedata (ASCTD) availablew No ASCT data availablen Far more common situationn General rule for conventional aminoglycosidetherapy (Assume adult with normal renal function)l Daily dose for gentamicin or tobramycin ~ 5 mg/kg/dw Amount per dose ~ 1.5 mg / kg or Single Dose Strategyl Daily dose for amikacin ~ 15 mg/kg/dw Amount per dose ~ 5 to 7.5 mg / kgEvaluating Aminoglycoside Dose &Interval without ASCTDw Parameters required forevaluation:n Agen Height in inchesn Weightn Serum creatinine3Evaluating Aminoglycoside Dose &Interval without ASCTDw Patient weight:n Actual body weight (ABW)n Lean body weight (LBW) in Kgl Males = 50 + 2.3 (# inches over 5 feet)l Female = 45 + 2.3 (# inches over 5 feet)l Note if LBW > ABW use ABWn Dosing body weight (DBW)l For patients >30% over LBWl DBW = LBW + 0.4 (ABW – LBW)Evaluating Aminoglycoside Dose &Interval without ASCTDw Calculated Creatinine Clearance(Crcl) inml/minn Method of Cockcroft and Gaultn Male = ((140 – Age )* LBW) / (72* Scr)n Female = 0.85 (Male)w Transform Crcl into Kd using Detli methodn Kd (Hr-1) = 0.0024 (Crcl) + 0.01w Transform Estimated Kd into T1/2n T1/2(Hrs) = 0.693 / KdCritical Evaluation ofCalculated Parametersw LBWn Para or Quadraplegic patient or where LBW > ABWw Creatinine Clearance (Crcl) this is an estimaten Elderlyn Para or Quadraplegic patientn Nutritionally starved patientsn Crcl not likely a linear function < 30 ml/minw Cautionn Dehydration or Overhydrationn Bleedingn Going into or coming out of acute renal failure4Initial Evaluation for ConventionalAminoglycoside Therapyw Peak concentrations should be ~ 10 x MIC of thelikely bacterial pathogenw Troughs should be as low as possible given thecircumstances surrounding the patientw Dose should be evaluated on a mg/kg/day basisand mg/kg per dose basis using the appropriatebody weight parameterw Dosing interval should be ~ 2 to 3 T1/2’s plus thehour for drug infusionw Try to limit total course of therapy to < 5 days toreduce risk of nephrotoxicity or ototoxicitySetting up Levels for TDMw General requirements are that patient’s renalfunction and fluid status be stablew Trough / Peak Optionn Patient must be at steady statel Received drug for 3-5 T1/2’sn If t1/2 is short in relation to doing interval, thelikelihood of having measurable trough is lown Nurse has administered drug on time and on scheduleduring the 3 to 5 T1/2 periodn Note: If patient seriously ill with impaired renalfunction, clinician may not be able to wait for steadystateSetting up Levels for TDMw Pharmacokinetic Series Optionn Patient does not have to be at steady staten Need to obtain trough level if not the firstdosen Need a minimum of 2-3 levels post antibioticinfusion spaced over a period of > 1.5 T1/2’s5Pharmacokinetic Studiesw Need to know the start and stop time of theaminoglycoside infusionn Drug must be administered at a constant raten Infusion should include tubing flushw Need to know the exact time when levels weredrawn in relation to dosew Should always critically evaluate the half-lifeand distribution volume generated from thepharmacokinetic studyn Factor in likely renal function, obesity, etc vs resultDosage Recommendationsw Should always factor in the clinical condition ofthe patientw The likely bacterial pathogen and level ofsensitivity to chosen aminoglycosidew The location of infection and how well theaminoglycoside is likely to concentrate at thatsitew Anticipate futuren Renal & fluid statusn Likely duration of therapyMonitoring Planw Patient status, patient location, temperature andbody weightw Day to day clinical statusw Culture information n Both positive & negative results from all sitesw WBC, BUN / Scr & other lab studiesw X-rays or scansw Fluid status, urine output, & ability to takeorally food or medicationsw Charting of doses and recording of levels6Critical Evaluationw Interpret data in relation to patientw Result real vs artifact (most often the problem)n Volume is a dose sensitive parameterl Preparation, administration or serum level handling errorw Less drug than thought increases volumew More drug than thought reduces volumel Obese vs wasting, para/quadriplegic, 3rd spacing (pleuraleffusion, ascites etc) or overhydration (anasarca)l Stable fluid status vs massive IV fluids &/or blood productsl May be a function of assay usedn Half-life is a dose independent parameterl Method used trough/peak vs series pharmacokineticsl Young vs old, NRF vs ARFl Beta-lactam inactivationCritical Evaluationw Double check entry of all data and calculationsw Evaluate final recommendation on basis of mgper Kg per dose and per dayw Before making recommendation to physician orin writing make sure patient data matches upwith the chartw Therapy should always be goal directed withmonitoring plan for drug efficacy and
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