Tables and Figures

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

Age in years Mean (Range)	n	Aminoglycoside	t½ (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 ± 0.12^A	123 ± 46^B	151	Trauma patients
29 (18-60)	10	Amikacin	1.40 ± 0.41	0.21 ± 0.08	78.6 ± 12.1^B	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)	t½ (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	26^A	Gentamicin	0.3192 ± 0.1511	NA	0.5186 ± 0.1445	NA	154	Suspected or confirmed bacterial infection
43 months	26^B	Gentamicin	0.2997 ± 0.1064	NA	0.4939 ± 0.1136	NA	154
(10-14 years)	7^A	Tobramycin	NA	2.37 ± 0.37	0.43 ± 0.09	3.67 ± 0.82^C	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).