Professional Documents
Culture Documents
ADJUSTMENT
Group 4 :
Florence Clay Mora Sirait 1411011050
Puji Rahmi Sumarno 1411011051
Katrin Dayatri 1411011052
Dyra Eka Aulia Khaidir 1411011055
Ghina Fadhilah 1411011068
INTRODUCTION
Exceeding peak steady-state conc. (> 1214 g/mL or 3540 g/mL for
amikacin) leads to an increased risk of ototoxicity (permanent auditory and
vestibular damage)
Aminoglycosides accumulate in the lymph of the inner ear causing ongoing
damage to cochlear or vestibular sensory cells
Difficult to early detect
Audiometry is required to detect high-tone hearing loss
The rst sign of auditory ototoxicity is tinnitus. Vestibular ototoxicity results
in the loss of balance, headache, ataxia, nausea, vomiting, nystagmus, and
vertigo.
THERAPEUTIC AND TOXIC
CONCENTRATION (cont.)
Trough steady state conc. above 23 g/mL or 10 g/mL for amikacin will lead
to nephrotoxicity
Aminoglycoside accumulate in the proximal tubular cells decrease the
ability of the kidney to concentrate urine decrease glomerular ltration
Occur before 35 days of therapy with proper dosing of the antibiotic
Patient usually critically ill, other sources of nephrotoxicity e.g. hypotension,
etc should be ruled out
Usually reversible
THERAPEUTIC AND TOXIC
CONCENTRATION (cont.)
Extended-Interval Dosing
Nephrotoxicity and ototoxicity also occurred just like conventional dosing bu
there is no increasing risk of toxicity
Using of this method only for selected patients such us Pseudomonas
aeruginosa infections where the organism has an expected MIC 2 g/mL,
peak concentrations between 20 and 30 g/mL and trough concentrations <1
g/mL
Differential Toxicity Among Aminoglycosides
Some clinicians believe that tobramycin is less nephrotoxic than gentamicin
or amikacin
CLINICAL MONITORING
PARAMETERS
DOSAGE COMPUTATION
INITIAL DOSAGE DETERMINATION
METHODS (cont.)
Recommended method
Usually, the AUC method is used with extended-interval aminoglycoside dosing
The steady-state area under the concentration-time curve during the dosage interval
(AUCss) is computed using the following equation
The dose is adjusted to attain the target AUCss using linear pharmacokinetics:
D new = (AUCss,new / AUCss,old) D old
BAYESIAN PHARMACOKINETIC COMPUTER
PROGRAMS
The most reliable computer programs use a nonlinear regression algorithm that incorporates
components of Bayes theorem
Briey, the patients drug dosage schedule and serum concentrations are input into the
computer.
The computer program has a pharmacokinetic equation preprogrammed for the drug and
administration method (oral, intravenous bolus, intravenous infusion, etc.).
Typically, a one-compartment model is used, although some programs allow the user to
choose among several different equations.
Using population estimates based on demographic information for the patient (age, weight,
gender, renal function, etc.) supplied by the user, the computer program then computes
estimated serum concentrations at each time there are actual serum concentrations.
Kinetic parameters are then changed by the computer program, and a new set of estimated
serum concentrations are computed
These pharmacokinetic parameters can then be used to compute improved dosing schedules
for patients
REFFERENCE
Bauer, Larry A. 2008. Applied Clinical Pharmacokinetics. USA: McGraw Hill Companies