Table 1. Pharmacokinetics of various aminoglycosides [mean SD ] among different adult patient populations receiving intravenous aminoglycoside therapy

Age in years

Mean (Range)

n

Aminoglycoside

t

(hr)

Vd

(L/Kg)

CLt (ml/min/kg)

Reference

Patient population

(60-79)

63

Gentamicin

2.4

0.26

1.31

5

Febrile patients treated for gram-negative bacterial infection

(20-39)

51

Gentamicin

2.2

0.23

1.29

5

 

(40-59)

59

Gentamicin

2.1

0.27

1.35

5

 

NA

6

Gentamicin

1.82 0.51

0.248 0.38

NA

144

Obese patients > 30% excess weight

NA

7

Tobramycin

1.80 0.23

0.297 0.64

NA

144

 

38 (16-92)

44

Gentamicin and Tobramycin

NA

0.41 0.12A

123 46B

151

Trauma patients

29 (18-60)

10

Amikacin

1.40 0.41

0.21 0.08

78.6 12.1B

124

Patients with normal kidney function

 

A Ideal body weight used

B ml/min/1.73m2

NA = Not available

 

 

 

Table 2. Pharmacokinetics of various aminoglycosides [mean SD ] among different pediatric patient populations receiving intravenous aminoglycoside therapy

 

Age

Mean (Range)

n

Aminoglycoside

Ke

(hr-1)

t

(hr)

Vd

(L/kg)

CL (ml/min/kg)

Reference

Patient Population

(9months to 15 years)

33

Gentamicin and Tobramycin

NA

2.32 0.65

0.32 0.07

1.71 0.53

74

Bone marrow transplant patients

45 months

26A

Gentamicin

0.3192 0.1511

NA

0.5186 0.1445

NA

154

Suspected or confirmed bacterial infection

43 months

26B

Gentamicin

0.2997 0.1064

NA

0.4939 0.1136

NA

154

 

(10-14 years)

7A

Tobramycin

NA

2.37 0.37

0.43 0.09

3.67 0.82C

84

Cystic fibrosis patients

(0.5- 4 years)

8

Gentamicin

0.31 0.01

NA

0.43 0.03

NA

4

 

(5-10 years)

11

Gentamicin

0.37 0.01

NA

0.35 0.01

NA

4

 

11-18 years)

12

Gentamicin

0.37 0.01

NA

0.32 0.01

NA

4

 

A Once-daily administration

B Multiple-daily administration

C L/hr

NA = Not Available

 

 

Table 3. Therapeutic range and dosage for patients with normal renal function receiving conventional aminoglycoside multiple-dose regimens.

 

Therapeutic

Range (mg/ml)

 

Aminoglycoside

Peak

Trough

Dosage for Normal Renal Function

Gentamicin

6 - 10

< 2

1.7 - 2 mg/kg every 8 hours

Tobramycin

6 - 10

< 2

1.7 - 2 mg/kg every 8 hours

Netilmicin

6 - 10

< 2

1.7 - 2 mg/kg every 8 hours

Amikacin

15 - 35

< 5

5 mg/kg every 8 hours or 7.5 mg/kg every 12 hours

Streptomycin

15 - 30

< 5

Generally 1.0 g every 24 hours (range, 0.5 -2.0 g)

 

Table 4.  Selection of aminoglycoside maintenance dosing using the method of Sarubbi and Hull (1978).

Creatinine Clearance

(ml/minute)

Half-life

(hrs)

8 hr

Dose Interval

12 hr

Dose Interval

24 hr

Dose Interval

90

3.1

84%

-

-

80

3.4

80

91%

-

70

3.9

76

88

-

60

4.5

71

84

-

50

5.3

65

79

-

40

6.5

57

72

92%

30

8.4

48

63

86

25

9.9

43

57

81

20

11.9

37

50

75

17

13.6

33

46

70

15

15.1

31

42

67

12

17.9

27

37

61

10

20.4

24

34

56

7

25.9

19

28

47

5

31.5

16

23

41

2

46.8

11

16

30

0

69.3

8

11

21

 

Table 5.  Suggested once daily dosage requirements for patients with altered renal function. 

Aminoglycoside

Creatinine Clearance

(ml/minute)

Dosage Interval (hr)

Dose

(mg/kg)

Gentamicin/Tobramycin

> 80

24

5.0

 

70

24

4.0

 

60

24

4.0

 

50

24

3.5

 

40

24

2.5

 

30

24

2.5

 

20

48

4.0

 

10

48

3.0

 

Hemodialysis*

48

2.0

 

 

 

 

Amikacin

> 80

24

15

 

70

24

12

 

50

24

7.5

 

30

24

4.0

 

20

48

7.5

 

10

48

4.0

 

Hemodialysis*

48

5.0

Adapted from Gilbert DN, Bennett WM. Use of antimicrobial agents in renal failure. Infect Dis Clin North Am 1989;3:517-531. and Bennett (1989). 

*Administer post-hemodialysis

Figure 1. Chemical structure of the aminoglycosides and spectinomycin. Neomycin contains approximately equal amounts of neomycin B (R1 = H; R2 = CH2NH2) and neomycin C (R1 = CH2NH2; R2 =  H). Kanamycin is principally kanamycin A, as shown. Gentamicin is gentamicin C complex with roughly equal amounts of C1 (R1 = R2 = CH3), C1a (R1 = R2 = H), and C2 (R1 = CH3; R2 = H).  (Modified with permission from Gilbert DN. Aminoglycosides. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. New York: Churchill Livingstone, 1995:281.)

 

 

 

Figure 2. Structures of amikacin (i), gentamicin C1a (ii), and kanamycin B (iii). Arrows indicate sites of modification by resistance enzymes. Tobramycin is 3'-deoxykanamycin B.

 


 

 

Figure 3. Influence of drug concentration on the bactericidal activity of tobramycin, ciprofloxacin and ticarcillin. (Reprinted from permission from Craig WA, Ebert SC. Killing and regrowth of bacteria in vitro: a review. Scand J Infect Dis 1991; 74(Suppl):63-70. With permission.)

 

 


Figure 4. Antimicrobial pharmacodynamics: an integration of microbiologic activity and pharmacokinetics.

 


Figure 5. Simulated concentration versus time profile for once-daily (7 mg/kg q. 24 h) and conventional (1.5 mg/kg q. 8 h) regimens in patients with normal renal function.

 


 

Figure 6. Once-daily aminoglycoside nomogram for the assessment of dosing interval using a

7 mg/kg dose of gentamicin or tobramycin.  (Reprinted from Nicolau DP, Freeman CD, Belliveau PP, Nightingale CH, Ross JW, Quintiliani R. Experience with a once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents Chemother 1995;39:650-655. With permission).