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JAC Advance Access published online on March 15, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn102
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Disposition of valganciclovir during continuous renal replacement therapy in two lung transplant recipients

N. Perrottet1, C. Robatel1, P. Meylan2, M. Pascual3, J. P. Venetz3, J. D. Aubert3, M. M. Berger4, L. A. Decosterd1 and T. Buclin1,*

1 Division of Clinical Pharmacology and Toxicology, University Hospital (CHUV), Lausanne, Switzerland 2 Microbiology Institute, University Hospital (CHUV), Lausanne, Switzerland 3 Organ Transplantation Centre, University Hospital (CHUV), Lausanne, Switzerland 4 Department of Adult Intensive Care Medicine, University Hospital (CHUV), Lausanne, Switzerland

Received 21 November 2007; returned 20 January 2008; revised 31 January 2008; accepted 17 February 2008

* Corresponding author. Tel: +41-21-314-42-61; Fax: +41-21-314-42-66; E-mail: thierry.buclin{at}chuv.ch

Objectives: To determine whether valganciclovir 450 mg every 48 h for cytomegalovirus (CMV) prophylaxis provides appropriate ganciclovir exposure in solid organ transplant recipients during continuous renal replacement therapy (CRRT).

Patients and methods: Ganciclovir pharmacokinetics was intensively studied in two lung transplant recipients under valganciclovir 450 mg every 48 h over one dosing interval. In vitro experiments using blank whole blood spiked with ganciclovir further investigated exchanges between plasma and erythrocytes.

Results: Ganciclovir disposition was characterized by apparent total body clearance of 3.3 and 5.8 L/h, terminal half-life of 16.9 and 14.1 h, and apparent volume of distribution of 60.3 and 104.9 L in Patients 1 and 2, respectively. The observed sieving coefficient was 1.05 and 0.96, and the haemofiltration clearance was 3.3 and 3.1 L/h. In vitro experiments confirmed rapid efflux of ganciclovir from red blood cells into plasma, increasing the apparent efficacy of haemofiltration.

Conclusions: A valganciclovir dosage of 450 mg every 48 h appears adequate for patients under CRRT requiring prophylaxis for CMV infection, providing concentration levels in the range reported for 900 mg once daily dosing outside renal failure.

Key Words: haemofiltration , pharmacokinetics , renal failure , erythrocytes


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N. Perrottet, C. Csajka, M. Pascual, O. Manuel, F. Lamoth, P. Meylan, J. D. Aubert, J. P. Venetz, P. Soccal, L. A. Decosterd, et al.
Population Pharmacokinetics of Ganciclovir in Solid-Organ Transplant Recipients Receiving Oral Valganciclovir
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