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

Author address: 

Nantes, FR

Abstract: 

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
2013

abstract No: 

R2544

Full conference title: 

23rd European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 23rd (2013)