Abstract:
:Pharmacokinetic research in China on the use of voriconazole in critically ill adult patients with different pulmonary diseases remains to be explored. This study evaluated the population pharmacokinetics of the use of voriconazole (VRC) in critically ill patients to determine covariate effects on VRC pharmacokinetics by NONMEM, which could further optimize VRC dosing in this population. A one-compartment model with first-order absorption and elimination best fit the data, giving 4.28 L/h clearance and 93.4 L volume of distribution of VRC. The model variability, described as an approximate percentage coefficient of interindividual variability in clearance and volume of distribution, was 72.94% and 26.50%, respectively. A significant association between Cmin and drug response or grade 2 hepatotoxicity was observed (p=0.002, <0.001, respectively, 1.5-4.0 µg/mL) via logistic multivariate regression. Monte Carlo simulations at 100, 150, 200, and 250 mg dosage predicted effectiveness at 45.99%, 99.76%, 98.76%, and 67.75% within the 1.5-4.0 µg/mL range, suggesting that a 150 or 200 mg intravenous dose twice daily is best suited to achieve the target steady state trough concentration range in critically ill patients with pulmonary disease.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Chen W,Xie H,Liang F,Meng D,Rui J,Yin X,Zhang T,Xiao X,Cai S,Liu X,Li Ydoi
10.1248/bpb.b14-00768subject
Has Abstractpub_date
2015-01-01 00:00:00pages
996-1004issue
7eissn
0918-6158issn
1347-5215journal_volume
38pub_type
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