AAC Accepts, published online ahead of print on 2 September 2014 Antimicrob. Agents Chemother. doi:10.1128/AAC.03641-14 Copyright © 2014, American Society for Microbiology. All Rights Reserved.
1
Impact of hypoalbuminemia on voriconazole pharmacokinetics in adult critically ill
2
patients
3
Running title: Voriconazole pharmacokinetics and hypoalbuminemia
4
1
Kim Vanstraelen #, PharmD; 2Joost Wauters, MD, PhD; 1Ine Vercammen; ³Henriette de Loor;
5
4
Johan Maertens, MD, PhD; 5Katrien Lagrou, PharmD, PhD; 6Pieter Annaert, PharmD, PhD;
6
1
Isabel Spriet, PharmD, PhD.
8
1
Clinical Pharmacology and Pharmacotherapy
9
Department of Pharmaceutical and Pharmacological Sciences
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10
University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium
11 12
2
13
University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium
Clinical Department of General Internal Medicine, Medical Intensive Care Unit
14 15
3
16
Renal Transplantation
17
University Hospitals Leuven / KU Leuven, Herestraat 49, 3000 Leuven, Belgium
KU Leuven Department of Microbiology and Immunology, Laboratory of Nephrology and
18 19
4
20
University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium
Clinical Department of Haematology, acute leukaemia and stem cell transplantation unit
21 22 23 1
24
5
25
Department of Microbiology and Immunology
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University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium
Clinical Department of Laboratory Medicine
27 28
6
29
Drug Delivery and Disposition
30
KU Leuven , Herestraat 49, 3000 Leuven, Belgium
Department of Pharmaceutical and Pharmacological Sciences
31 32 33
# Correspondence to:
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Kim Vanstraelen, PharmD
35
Clinical Pharmacist,
36
Clinical Pharmacology and Pharmacotherapy
37
Department of Pharmaceutical and Pharmacological Sciences, Herestraat 49, 3000 Leuven
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E-mail: [email protected]
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Tel: 0032 16 34 23 39
40
Fax: 0032 16 34 30 85
41 42 43 44 45
2
46
Abstract
47
Setting the adequate dose for voriconazole is challenging due to its variable pharmacokinetics.
48
We investigated the impact of hypoalbuminemia (70% *- Median [IQR] Study A: Patients admitted to the ICU, treated with voriconazole Study B: Patients admitted to the ICU, not treated with voriconazole. Plasma spiked with 1.5; 2.9; 9 mg/L VRC = voriconazole; CRP= C-reactive protein AAG = alpha-1-acid-glycoprotein * day of sampling ** In study A, no coadministration of NSAIDs, phenytoin, valproic acid, coumarines or aspirin was documented. *** In study B, administration of aspirin was documented in 7 patients, acenocoumarol and phenytoin each in 1 patient. No coadministration of NSAIDs or valproic acid was documented. Reference values according to the University Hospitals Leuven.
1
Impact of hypoalbuminemia on voriconazole pharmacokinetics in adult critically ill
2
patients
3
Running title: Voriconazole pharmacokinetics and hypoalbuminemia
4
1
Kim Vanstraelen #, PharmD; 2Joost Wauters, MD, PhD; 1Ine Vercammen; ³Henriette de Loor;
5
4
Johan Maertens, MD, PhD; 5Katrien Lagrou, PharmD, PhD; 6Pieter Annaert, PharmD, PhD;
6
1
Isabel Spriet, PharmD, PhD.
8
1
Clinical Pharmacology and Pharmacotherapy
9
Department of Pharmaceutical and Pharmacological Sciences
7
10
University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium
11 12
2
13
University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium
Clinical Department of General Internal Medicine, Medical Intensive Care Unit
14 15
3
16
Renal Transplantation
17
University Hospitals Leuven / KU Leuven, Herestraat 49, 3000 Leuven, Belgium
KU Leuven Department of Microbiology and Immunology, Laboratory of Nephrology and
18 19
4
20
University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium
Clinical Department of Haematology, acute leukaemia and stem cell transplantation unit
21 22 23 1
24
5
25
Department of Microbiology and Immunology
26
University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium
Clinical Department of Laboratory Medicine
27 28
6
29
Drug Delivery and Disposition
30
KU Leuven , Herestraat 49, 3000 Leuven, Belgium
Department of Pharmaceutical and Pharmacological Sciences
31 32 33
# Correspondence to:
34
Kim Vanstraelen, PharmD
35
Clinical Pharmacist,
36
Clinical Pharmacology and Pharmacotherapy
37
Department of Pharmaceutical and Pharmacological Sciences, Herestraat 49, 3000 Leuven
38
E-mail: [email protected]
39
Tel: 0032 16 34 23 39
40
Fax: 0032 16 34 30 85
41 42 43 44 45
2
46
Abstract
47
Setting the adequate dose for voriconazole is challenging due to its variable pharmacokinetics.
48
We investigated the impact of hypoalbuminemia (70% *- Median [IQR] Study A: Patients admitted to the ICU, treated with voriconazole Study B: Patients admitted to the ICU, not treated with voriconazole. Plasma spiked with 1.5; 2.9; 9 mg/L VRC = voriconazole; CRP= C-reactive protein AAG = alpha-1-acid-glycoprotein * day of sampling ** In study A, no coadministration of NSAIDs, phenytoin, valproic acid, coumarines or aspirin was documented. *** In study B, administration of aspirin was documented in 7 patients, acenocoumarol and phenytoin each in 1 patient. No coadministration of NSAIDs or valproic acid was documented. Reference values according to the University Hospitals Leuven.
