Bioavailability and population pharmacokinetics of voriconazole in lung transplant recipients

Han, K., Capitano, B., Bies, R., Potoski, B.A., Husain, S., Gilbert, S., Paterson, D. L., McCurry, K. and Venkataramanan, R. (2010) Bioavailability and population pharmacokinetics of voriconazole in lung transplant recipients. Antimicrobial Agents and Chemotherapy, 54 10: 4424-4431. doi:10.1128/AAC.00504-10

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Author Han, K.
Capitano, B.
Bies, R.
Potoski, B.A.
Husain, S.
Gilbert, S.
Paterson, D. L.
McCurry, K.
Venkataramanan, R.
Title Bioavailability and population pharmacokinetics of voriconazole in lung transplant recipients
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 0066-4804
Publication date 2010-10
Sub-type Article (original research)
DOI 10.1128/AAC.00504-10
Open Access Status File (Publisher version)
Volume 54
Issue 10
Start page 4424
End page 4431
Total pages 8
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2011
Language eng
Formatted abstract
This study was undertaken to characterize the pharmacokinetics and bioavailability of voriconazole in adult lung transplant patients during the early postoperative period, identify factors significantly associated with various pharmacokinetic parameters, and make recommendations for adequate dosing regimens. Thirteen lung transplant patients received two intravenous infusions (6 mg/kg, twice daily [b.i.d.]) immediately posttransplant followed by oral doses (200 mg, b.i.d.) for prophylaxis. Blood samples (9/interval) were collected during one intravenous and one oral dosing interval from each patient. Voriconazole plasma concentrations were measured by high-pressure liquid chromatography (HPLC). NONMEM was used to develop pharmacokinetic models, evaluate covariate relationships, and perform Monte Carlo simulations. There was a good correlation (R2 = 0.98) between the area under the concentration-time curve specific for the dose evaluated (AUC 0-∞) and trough concentrations. A two-compartment model adequately described the data. Population estimates of bioavailability, clearance, Vc, and Vp were 45.9%, 3.45 liters/h, 54.7 liters, and 143 liters. Patients with cystic fibrosis (CF) exhibited a significantly lower bioavailability (23.7%, n = 3) than non-CF patients (63.3%, n = 10). Bioavailability increased with postoperative time and reached steady levels in about 1 week. Vp increased with body weight. Bioavailability of voriconazole is substantially lower in lung transplant patients than non-transplant subjects but significantly increases with postoperative time. CF patients exhibit significantly lower bioavailability and exposure of voriconazole and therefore need higher doses. Intravenous administration of voriconazole during the first postoperative day followed by oral doses of 200 mg or 400 mg appeared to be the optimal dosing regimen. However, voriconazole levels should be monitored, and the dose should be individualized based on trough concentrations as a good measure of drug exposure. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2011 Collection
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Citation counts: TR Web of Science Citation Count  Cited 30 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 33 times in Scopus Article | Citations
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Created: Fri, 18 Feb 2011, 13:05:36 EST by Caroline Irle on behalf of UQ Centre for Clinical Research