Aminoglycoside... TDM. 4.1 4.2 4.3 4.4. 5.1 5.2 5.3 sample time 5.4. 6.1-6.2 -. 7.1 7.2. /...
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)
TDM ( aminoglycoside) 3 (L/hr/kg) (L/kg) (hr) ( 4 weeks) 0.05 ± 0.01 0.45 ± 0.1 6 ± 2 20-40 hr (>4 week-1 year) 0.10 ± 0.05 0.40 ± 0.1 4 ± 1 15-15 hr (>1-13 years) 0.13 ± 0.03 0.35 ± 0.15 1.5 ± 1 3-12 hr (>13-18 years) 0.11 ± 0.03 0.30 ± 0.1 1.5 ± 1 3-12 hr (>18-60 years) 0.08 ± 0.03 0.30 ± 0.13 0.45 ± 0.1 5-15 hr (>60 years) 0.06 ± 0.03 3.5 ± 2 8-30 hr 40-60 8-12 days 10-20 5-8 1, 2, 4 4.1 Aminoglycoside (MDD) (mg/kg) Gentamicin Tobramycin 1.5-2 5 Amikacin Kanamycin 5-7.5 15 Streptomycin Netilmicin 1.3-3.25 6.5 (OD) (mg/kg) Neomycin-oral 1 gm 4 4 1gm 24 4-12 gm/day po MDD: Multiple daily dose OD Once daily dose
4.2 ( ) 1, 2 4.2.1 CrCl (ml/min) 90 84 % ( ) 8 12 24 80 80 % 91% 70 88 % 60 84 % 50 79 % 40 72 % 92 % 30 86 % 25 81% 20 75 % 17 70 % 15 67 % 12 61 % 10 56 % 7 47 % 5 41 % 2 30 % 4.2.2 (mg/kg/q24h) 2, 4 Aminoglycosdie Clcr (ml/min) 80 60-80 40-60 30-40 Gentamycin/Tobramycin 5.1 4 3.5 2.5 Amikacin/Streptomycin 15 12 7.5 4 Isepamicin 8 8 8 8 (q48h) Netilmicin 6.5 5 4 2
3, 5, 6 4.3 1. (Clcr 20 ml/min ) 2. 3. ( 20 %) 4. (Cystic fibrosis) 5. 3, 5, 6 4.3 1. / 2. Aminoglycoside (post-antibiotic) 3. 4. 1993 Lancet NAG (N-acetyl-beta-D-glucosaminidase) β-microglobulin NAG β-microglobulin 6 ( )
2, 3, 4 5.1 Aminoglycoside Gentamicin (mg/kg) (µg/ml) (µg/ml) MDD: 1.5-2 4-10 1-2 Tobramycin OD: 5 16-24 1 Amikacin Kanamycin Streptomycin Netilmicin MDD: Multiple daily dose OD Once daily dose MDD 5-7.5 15-30 5-10 OD: 15 56-64 1 MDD: 1.3-3.25 4-12 1-2 OD: 6.5 23-30 1 2, 3 5.2 Aminoglycosidey Aminoglycosidey aminoglycoside (1) (2) (3) ( BUN Scr ) ( ICU )
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) 13 12 11 10 9 8 7 6 5 4 3 2 Q48h Q36h Q24h 6 7 8 9 10 11 12 13 14
3, 7 5.4 IBW male 50 + 2.3 (cm/2.54) 60 IBW male 45.5 + 2.3 (cm/2.54) 60 AdjBW IBW + 0.4 (TBW-IBW) Clcr male (140-age) Kg 72 Scr Clce female estimated Clcr male 0.85 t 1/2 0.693/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, 8 6.1 aminoglycoside 25 % 25-50 % ( ) IBW AdjBW 13 % 11 % 40 % 38 %
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
1, 2, 3 7.1 ( ) Gentamicin ( ) peak 12 mg/l trough 2 mg/l ( ) AAmikacin ( ) peak 20-35 mg/l trough 8 mg/l 7.2 9 / 1. antihistamines epinephrine., ECG monitoring IV urine output (3 to 6 ml/kg/hr) 2. (3-6 ml/kg/hr) 3. 4. 5. 1, 2 1. BUN 2. Cisplatin, Enviomycin, Cyclosporin, Amphotericin B, Vancomycin, Polymycin B 3. Penicillin aminoglycoside aminoglycoside
4. 30 60 30 1. Drug Information Handbook. 9 th ed., p55-56, 564-566 (2001-2002). 2. Aminoglycoside. In: Drugdex Informaction System, Micromedex, Inc.; 2003. 3. Anderson DM, Tallian KB. Aminoglycoside, 2nd ed. Murphy, JE: Clinical Pharmacokinetics Pocket Reference. 23-59, 2001. 4. Guide to antimicrobial therapy. 32 th ed., p71, 125, 2002.. 5. 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, 1995. 6. Gonzalez P. Aguado JM. Martin MA. Fernandez-Chacon T. Ortuno B. Once-daily aminoglycoside dosing. Lancet. 341(8849): 895, 1993. 7. Edson RS. Terrell CL. The aminoglycosides. Mayo Clinic Proceedings. 74(5): 519-28, 1999. 8. Udall JA: Drug interference with warfarin therapy. Clinical Medicine.77:20-25, 1970. 9. Aminoglycoside. In: ToxPoints System, Micromedex, Inc.; 2003.