Intravenous voriconazole pharmacokinetics five days after lung transplantation in cystic fibrosis- and non-cystic fibrosis patients

G. Deslandes*, T. Lepoivre, R. Bouquié, E. Dailly, H. Grison-Hernando, M. Treilhaud, P. Jolliet


Objectives: For patients with Aspergillus Spp isolated from their respiratory secretions prior to undergoing transplantation, a prophylactic antifungal therapy was started on the day of transplantation. Patients received a combination of caspofungin (50mg once daily) and voriconazole (4mg/kg twice daily). When voriconazole optimal blood level (1mg/L) is reached, caspofungin is stopped. The objective of this work was to study voriconazole pharmacokinetics in this population and to propose an adequate dosing regimen. Methods: Our voriconazole local therapeutic drug monitoring program for lung transplant patient included a pharmacokinetic profiles obtained on day 5 post-transplant. Sampling time was done just prior and at end of the infusion (0h=Cmin), 1h=Cmax) and at 3h, 5h and 12h. Individual Pharmacokinetic parameters (Area Under curve (AUC), volume of distribution (Vd), Clearance and Elimination Half-life (T1/2)) were calculated using a 2 compartmental model. We retrospectively analyzed the data collected from October 2011 to September 2012 in two patient groups (cystic fibrosis/no cystic fibrosis). The measured variables were compared between cystic fibrosis and other patients by student’s t-test. Statistical significance was defined by p-value inferior to 0.05. Results: Cystic fibrosis patients were significantly younger than others patients. Weigh, dosage regimen, time after lung transplant were not different in the 2 groups. The interindividual variability of voriconazole pharmacokinetics is high. Individual PK parameters were statistically different in the two groups. Conclusion: Pharmacokinetic of voriconazole is widely influenced by cystic fibrosis after lung transplantation with a significant increase in clearance and decrease in Cmin, Cmax, AUC, half-life and Vd. Recommended twice daily dose of 6 mg/kg for the first 24 hours followed by 4 mg/kg can’t lead in these patients to through concentrations of 1 mg/L. As recommended by Han et al.(1) for cystic fibrosis patients, intravenous infusion of 6 mg/kg twice daily during the first post-operative days and the use of through concentration in order to quickly individualize voriconazole dose could be a way to follow. (1): Antimicrob Agents Chemother. 2010 October; 54(10): 4424–4431. Bioavailability and Population Pharmacokinetics of Voriconazole in Lung Transplant Recipients. K. Han, B. Capitano, R. Bies, B. A. Potoski, S. Husain, S. Gilbert, D. L. Paterson,K. McCurry, and R. Venkataramanan

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23rd European Congress of Clinical Microbiology and Infectious Diseases