1, 2 Aminoglycoside G( ) (pseudomonas aeruginosa) (E coli) (Enterobacter) aminoglycoside aminoglycoside amikacin gentamycin tobramycin streptomycin (

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1 Aminoglycoside... TDM sample time /...

2 1, 2 Aminoglycoside G( ) (pseudomonas aeruginosa) (E coli) (Enterobacter) aminoglycoside aminoglycoside amikacin gentamycin tobramycin streptomycin ( ) streptomycin (tuberculosis) (plaque) (tularemia) penicillin streptococcus viridans neomycin 1, 2 Aminoglycoside aminoglycoside 30 S 30 S (polysome) Aminoglycoside β-lactam aminoglycoside Neomycin (ammonia forming bacteria)

3 TDM ( aminoglycoside) 3 (L/hr/kg) (L/kg) (hr) ( 4 weeks) 0.05 ± ± ± hr (>4 week-1 year) 0.10 ± ± ± hr (>1-13 years) 0.13 ± ± ± hr (>13-18 years) 0.11 ± ± ± hr (>18-60 years) 0.08 ± ± ± hr (>60 years) 0.06 ± ± hr days , 2, Aminoglycoside (MDD) (mg/kg) Gentamicin Tobramycin Amikacin Kanamycin Streptomycin Netilmicin (OD) (mg/kg) Neomycin-oral 1 gm 4 4 1gm gm/day po MDD: Multiple daily dose OD Once daily dose

4 4.2 ( ) 1, CrCl (ml/min) % ( ) % 91% % % % % 92 % % 25 81% % % % % % 7 47 % 5 41 % 2 30 % (mg/kg/q24h) 2, 4 Aminoglycosdie Clcr (ml/min) Gentamycin/Tobramycin Amikacin/Streptomycin Isepamicin (q48h) Netilmicin

5 3, 5, (Clcr 20 ml/min ) ( 20 %) 4. (Cystic fibrosis) 5. 3, 5, / 2. Aminoglycoside (post-antibiotic) Lancet NAG (N-acetyl-beta-D-glucosaminidase) β-microglobulin NAG β-microglobulin 6 ( )

6 2, 3, Aminoglycoside Gentamicin (mg/kg) (µg/ml) (µg/ml) MDD: Tobramycin OD: Amikacin Kanamycin Streptomycin Netilmicin MDD: Multiple daily dose OD Once daily dose MDD OD: MDD: OD: , Aminoglycosidey Aminoglycosidey aminoglycoside (1) (2) (3) ( BUN Scr ) ( ICU )

7 5.3 sample time 3, 5 Aminoglycoside 1. ( ) 3 (1) 30 (2) ( ) Q8h 1, 5 Q12h 1, 5, 8 Q24h 2, 12 ( ) 5 2. (1) 8-10 (2) ( ) 14 (µg/ml) Q48h Q36h Q24h

8 3, IBW male (cm/2.54) 60 IBW male (cm/2.54) 60 AdjBW IBW (TBW-IBW) Clcr male (140-age) Kg 72 Scr Clce female estimated Clcr male 0.85 t 1/ /k k ln (Cp 2 /Cp 1 )/ T Cmax extrapolated Cp measured/ e -kt Cmin extrapolated Cp measured/ e -kt (t = time since end of infusion) (t = time until start of next infusion) τ -1/k [ln (desired trough/ desired peak)] + t t τ New dose k Vd desired peak (1- e -kτ / 1- e -kt ) 1, 2, 3, aminoglycoside 25 % % ( ) IBW AdjBW 13 % 11 % 40 % 38 %

9 Aminoglycoside ( streptomycin kanamycin ) amikacin gentamycin netilmicin tobramycin 6.2 NSAIDs Amphotericin B Cisplatin Vancomycin Penicillin Nondepolarizing muscale relaxant Warfarin aminoglycoside NSAIDs aminoglycoside aminoglycoside Penicillin Aminoglycoside Penicillin Aminoglycoside Aminoglycoside Neomycin K prothrombin time INR warfarin

10 1, 2, ( ) Gentamicin ( ) peak 12 mg/l trough 2 mg/l ( ) AAmikacin ( ) peak mg/l trough 8 mg/l / 1. antihistamines epinephrine., ECG monitoring IV urine output (3 to 6 ml/kg/hr) 2. (3-6 ml/kg/hr) , 2 1. BUN 2. Cisplatin, Enviomycin, Cyclosporin, Amphotericin B, Vancomycin, Polymycin B 3. Penicillin aminoglycoside aminoglycoside

11 Drug Information Handbook. 9 th ed., p55-56, ( ). 2. Aminoglycoside. In: Drugdex Informaction System, Micromedex, Inc.; Anderson DM, Tallian KB. Aminoglycoside, 2nd ed. Murphy, JE: Clinical Pharmacokinetics Pocket Reference , Guide to antimicrobial therapy. 32 th ed., p71, 125, Nicolau DP, Freeman CD, Belliveau PP. Experience with a once-daily aminoglycoside program administered to 2184 adult patients. Antimicrob Agents Chemotherapy. 39(3): 650-5, Gonzalez P. Aguado JM. Martin MA. Fernandez-Chacon T. Ortuno B. Once-daily aminoglycoside dosing. Lancet. 341(8849): 895, Edson RS. Terrell CL. The aminoglycosides. Mayo Clinic Proceedings. 74(5): , Udall JA: Drug interference with warfarin therapy. Clinical Medicine.77:20-25, Aminoglycoside. In: ToxPoints System, Micromedex, Inc.; 2003.

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