PMID- 26062298
OWN - NLM
STAT- MEDLINE
DCOM- 20150921
LR  - 20161125
IS  - 0031-7144 (Print)
IS  - 0031-7144 (Linking)
VI  - 70
IP  - 5
DP  - 2015 May
TI  - A pharmacokinetic/pharmacodynamic analysis of a standard voriconazole regimen in 
      different CYP2C19 genotypes by Monte Carlo simulation.
PG  - 306-9
AB  - OBJECTIVES: The objective of this study was to evaluate the standard voriconazole 
      dosage regimen (maintenance dose was 200 mg bid orally) against Aspergillus 
      infections in different CYP2C19 genotypes from a pharmacokinetic/pharmacodynamic 
      (PK/PD) perspective. METHOD: Monte Carlo simulation (MCS) was applied to simulate 
      5,000 patients by integrating published pharmacokinetic (PK) parameters, 
      variability of PK parameters on CYP2C19 genotypes and microbiological data. 
      RESULTS: The standard dosage regimen for poor metabolizers (PM) with Aspergillus 
      infections was effective except A. versicolor, for heterozygous extensive 
      metabolizers (HEM), Aspergillus fumigatus, A. terreus and A. nidulans infections 
      could be treated effectively with the standard dosage regimen; for extensive 
      metabolizers (EM), the standard voriconazole dosage regimen failed to achieve the 
      best outcome for the six Aspergillus spp. Increasing dose (e.g. 300 mg bid) or 
      even changing the antifungal drug was needed for EM and most HEM patients with 
      Aspergillus infection. CONCLUSION: Instead of using a standard dosage regimen for 
      all patients, the voriconazole dosage regimen needs to be optimized for patients 
      with different CYP2C19 genotypes.
FAU - Liao, Shasha
AU  - Liao S
FAU - Ge, Tingyue
AU  - Ge T
FAU - Zhu, Liqin
AU  - Zhu L
FAU - Zhao, Yang
AU  - Zhao Y
FAU - Yang, Jianwei
AU  - Yang J
FAU - Xu, Gaoqi
AU  - Xu G
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Pharmazie
JT  - Die Pharmazie
JID - 9800766
RN  - 0 (Antifungal Agents)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
RN  - JFU09I87TR (Voriconazole)
SB  - IM
MH  - Algorithms
MH  - Antifungal Agents/administration & dosage/*pharmacokinetics/*pharmacology
MH  - Aspergillus/drug effects
MH  - Computer Simulation
MH  - Cytochrome P-450 CYP2C19/*genetics
MH  - Genotype
MH  - Humans
MH  - Microbial Sensitivity Tests
MH  - Monte Carlo Method
MH  - Precision Medicine
MH  - Voriconazole/administration & dosage/*pharmacokinetics/*pharmacology
EDAT- 2015/06/13 06:00
MHDA- 2015/09/22 06:00
CRDT- 2015/06/12 06:00
PHST- 2015/06/12 06:00 [entrez]
PHST- 2015/06/13 06:00 [pubmed]
PHST- 2015/09/22 06:00 [medline]
PST - ppublish
SO  - Pharmazie. 2015 May;70(5):306-9.