Pharmacokinetics of CRRT

and Fatemeh Ghane Sharbaf2

(1)
Department of Pediatrics Section of Nephrology, Rush University Medical Center, Chicago, IL, USA
(2)
Department of Pediatrics Section of Nephrology, Mashhad University of Medical Sciences, Mashhad, Iran
 

Drug Removal During CRRT: Basic Principles

Appropriate drug dosing in the acute kidney injury (AKI) patient treated with continuous renal replacement therapies (CRRT) is an important consideration to optimize therapeutic outcomes and to minimize drug toxicity [1–3]. Underdiagnosed and untreated AKI may lead to chronic kidney disease and end-stage renal disease [4]. When adjusting drug doses for the AKI patient, drug doses should be adjusted based on the renal and CRRT clearance of the drug, the degree of renal impairment, and the potential nephrotoxicity of the prescribed drug. The sum of renal creatinine clearance and CVVH ultrafiltration provides a starting point for subsequent antibiotic dosing. Medication dosing for children with AKI needs to be individualized based on pharmacokinetics and pharmacodynamics principles of the prescribed drugs whenever possible [5–11]. Both the volume of distribution and half-life of several drugs are markedly increased in the presence of AKI, and thus larger loading doses may need to be administered to achieve the target serum concentration. It is also necessary to know the degree of protein binding and the half-life of the concerned drug. Because of the presence of a positive fluid balance in the early stages of AKI, the dosing regimen for many drugs, especially antimicrobial agents, should be initiated at normal dosage regimens. When available, therapeutic drug monitoring should be used, especially for drugs with low therapeutic index. Guidelines whether or not dose adjustment is required for children with AKI is provided in Table 5.1.
Table 5.1
Pediatric drug dosage adjustments during continuous veno-venous hemofiltration (CVVH)a
Drug category
Protein binding (%)
SC
V d L/kg
t 1/2 h
Normal dose (GFR 100)
Dose in CVVH <1–2 L/h GFR < 15–30
Analgesic
Acetaminophen
20–50
0.93
0.2–0.4
2–3
5 mg/kg iv q8h
No change
Acetylsalicylic
>99
50
0.25
0.8
10 mg/kg q4–6h
No change
Codeine
7
NA
3–6
3
0.5–1 mg/kg q6h
75 % dose reduction
Ibuprofen
90–99
NA
0.14
1.8
5–10 mg/kg q6h
No change
Ketorolac
>99
NA
0.1–0.3
5
0.25–1 mg/kg q6h
No change
Fentanyl
80–85
0.29
2.4
2.6
1–5 mcg/kg q6h
75 % dose reduction
Meperidine
60–85
NA
2.4
11
0.5–2 mg/kg infusion
75 % dose reduction
Methadone
60–90
NA
4.5
8–49
0.5 mg/kg q6h
0.5 mg/kg q24h
Morphine
20–35
0.65
3.3
2.5
0.05–0.2 mg/kg iv q2–4h
75 % dose reduction
Antibiotics
Aciclovir
9–33
0.85
0.7
2–3
10 mg/kg iv q8h
Normal dose iv q24h
Amikacinb
<20
0.95
0.2–0.7
1.6-2.5
20 mg/kg (max 1.5 g) iv q24h
10 mg/kg iv q24h
Amoxicillin
15–20
0.85
1.3
5–20
5–15 mg/kg iv q8h
No change
Amphotericin liposomal
90
NA
0.1–0.4
6–10
3–5 mg/kg iv q24h
No change
Ampicillin
17–20
0.8
0.32
1–1.8
50 mg/kg iv q8h
No change
Azithromycin
10–50
NA
NA
6–8
5 mg/kg q12
No change
Aztreonam
50–60
NA
0.25
2
80–120 mg/kg q8h
No change
Benzylpenicillin
60
NA
0.3–0.4
0.5–1.2
25–50 mg/kg iv in q8h
No change
Cefaclor
20–50
NA
0.24–0.35
1
10–20 mg/kg iv q12h
No change
Cefazolin
70–86
NA
0.13–0.22
2
50–100 mg/kg iv q8h
505 dose reduction
Cefotaxime
40
NA
0.3
1.5
50 mg/kg iv q8–12h
No change
Ceftazidime
<10
NA
0.2–0.4
1
25 mg/kg iv q8h
No change
Ceftriaxone
85–95
0.66
0.35
8
80 mg/kg (max 2 g) iv q24h
No change
Cefuroxime
33
0.66
0.19
1.5
25–50 mg/kg iv q8h
25–50 mg/kg iv q12–24 h
Cidofovir
<10
NA
0.3
15–25
5 mg/kg iv q 1–2 weeks
2 mg/kg iv q1-2 weeks
Ciprofloxacin
20–40
0.7
2–3
4–5
10 mg/kg (max 400 mg) iv q12h
25 % reduction q 12 h
Clindamycin
>90
0.4
0.6–1.2
2–3
5–10 mg/kg (max 1.2 g) iv q6h
No change
Co-amoxiclav (amoxicillin + clavulanic acid)
17–30
NA
0.2–0.4
0.9
30 mg/kg (max 1.2 g) iv q8h
50 % dose reduction
Co-trimoxazole (trimethoprim + sulfamethoxazole)
50–66
NA
0.3–2.2
5.5–17
40–60 mg/kg ivq12h
50 % dose reduction
Erythromycin
70–95
0.3
0.6–1.2
2
12.5–25 mg/kg iv q6h
No change
Flucloxacillin
95
NA
0.13
2–3
25–100 mg/kg iv q8h
No change
Fluconazole
12
NA
0.6–1.2
15–20
6–12 mg/kg iv q72h
No change
Ganciclovir
1–2
0.84
0.4–0.8
3–28
5 mg/kg iv q12h
50 % dose reduction
Gentamicinb
1–30
0.95
0.2–0.5
1–3
7 mg/kg iv q24h
4 mg/kg iv q24h
Imipenem
13–21
1
0.5
1–1.3
15 mg/kg (max 500 mg) iv q6h
25 % dose reduction
Isoniazid
10–15
NA
NA
2.8
10–15 mg/kg q12–24h
No change
Ketoconazole
85–99
NA
2–4
8
3–6 mg/kg q24h
No change
Levofloxacin
25–38
0.8
NA
NA
5–10 mg/kg q24h
No change
Meropenem
2
NA
0.4
1.5–2.3
10–20 mg/kg iv q8h
No change
Metronidazole
<20
0.8
1.1
6–12
7.5 mg/kg (max 500 mg) iv q8h
No change
Nafcillin
90
0.2
0.35
1
15–50 mg/kg iv q4–6h
No change
Flaxacillin
20–30
NA
NA
NA
15 mg/kg iv q12h
No change
Piperacillin
20–30
NA
0.2
0.7
200 mg/kg q4h
200 mg/kg q8h
Rifampicin
80
0.2
0.66
1–3.8
10 mg/kg (max 500 mg) iv q12h
No change
Streptomycin
34
NA
NA
5–8
20–40 mg/kg iv q24h
7.5 mg/kg q24h
Ticarcillin
45–65
NA
0.22
1.1
80 mg/kg (max 3.2 g) q8h
No change
Tobramycin
44–50
1.6
1.6
11
60 mg/kg iv q12h
50 % dose reduction
Vancomycinb
55
NA
0.4–0.7
5.6
15 mg/kg iv q8h
10 mg/kg iv q12h
Anticoagulants
Heparinc
95
<0.1
1
2
10–25 U/kg/h
No change
Warfarin
>90
0.02
0.05
50
0.5–8 mg q24h
No change
Anticonvulsants
Carbamazepine
75–90
74
0.25
1.3
5–10 mg/kg q12h
75 % dose reduction
Phenobarbital
30–50
0.6
0.8
80
3–7 mg/kg q24h
10 mg/kg q 6-8 h
Phenytoin
80–90
0.1
0.6
20
3–7 mg/kg q8h
No change
Valproic acid
80–93
0.1
0.2–1
9–16
10–30 mg/kg q12h
No change
Antihistamines
Cimetidine
19
0.8
1
2
4–8 mg/kg q12h
50 % dose reduction
Diphenhydramine
78
NA
3–6
5–11
1 mg/kg q4–6h
No change
Famotidine
15–20
NA
1–1.5
2–4
0.5 mg/kg q12h
No change
Terbutaline
25
NA
1.6
5.7
0.1–0.4 mg/kg/min iv infusion
No change
Antihypertensive agents
Amlodipine
93
NA
21
40
0.05–0.17 mg/kg q24h
No change
Captopril
30
NA
1.5
1.5
0.1–0.5 mg/kg q6–8h
75 % dose reduction
Clonidine
20–40
0.7
2.1
8
2.5–5 mcg/kg q12h
No change
Enalapril
<50
0.5
1.7
11
0.1 mg/kg q12h
75 % dose reduction
Hydralazine
85–90
        
0.15 mg/Kg q8h
Isradipine
95
0.13
1.5
1
0.05–0.2 mg/kg q8h
No change
Labetalol
50
      
0.4–3 mg/h iv infusion
No change
Lisinopril
25
NA
NA
5–6
0.1 mg/kg q12–24h
0.50 % dose reduction
Nifedipine
95 %
0.08
1.2
2.8
0.25–0.5 mg/kg q6–8h
No change
Prazosin
95
0.03
0.6
2.9
0.2–1 mg/kg q12h
No change
Propranolol
60–90
0.07
4.3
3.5
0.1–1 mg/kg q6h
No change
Cardiovascular agents
Amiodarone
96
0.03
61
N/A
5–10 mg/kg q24h
No change
Atenolol
<5
1
0.43
6
1–2 mg/kg q24h
No change
Atropine
14–22
0.5
2.9
2–4
0.5–1 mg q5–30min
No change
Digoxin
20–55
0.8
6.5
40
250 mcg q24h
62.5 mcg q24h
Dobutamine
NA
NA
0.2
2
2–20 mcg/kg/min iv infusion
No change
Dopamine
NA
NA
NA
5.5
2–20 mcg/kg/min iv infusion
No change
Epinephrine
N/A
NA
<0.1
<0.1
0.01–1 mcg/kg/min iv infusion
No change
Milrinone
70
NA
0.38
2.3
0.25–0.75 mcg/kg/min iv infusion
0.33 mcg/kg/min iv infusion
Procainamide
15–20

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Related posts:

  1. Case Management
  2. Introduction: Acute Kidney Injury and Continuous Renal Replacement Therapy
  3. CRRT Prescription
  4. Continuous Renal Replacement Therapy (CRRT)

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Jul 3, 2016 | Posted by in PEDIATRICS | Comments Off on Pharmacokinetics of CRRT

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