PMID- 24914120
OWN - NLM
STAT- MEDLINE
DCOM- 20150828
LR  - 20211021
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 58
IP  - 8
DP  - 2014 Aug
TI  - Population pharmacokinetic-pharmacodynamic analysis of voriconazole and 
      anidulafungin in adult patients with invasive aspergillosis.
PG  - 4727-36
LID - 10.1128/AAC.02809-13 [doi]
AB  - To evaluate the exposure-response relationships for efficacy and safety of 
      voriconazole and anidulafungin in adult patients with invasive aspergillosis 
      (IA), a population pharmacokinetic-pharmacodynamic (PK-PD) analysis was performed 
      with data from a phase 3, prospective, double-blind, comparative study evaluating 
      voriconazole and anidulafungin combination therapy versus voriconazole (and 
      placebo) monotherapy. Anidulafungin/placebo treatment duration was 2 to 4 weeks, 
      and voriconazole treatment duration was 6 weeks. Efficacy (6-week all-causality 
      mortality and 6-week global response [n = 176]) and safety (hepatic [n = 238], 
      visual [n = 199], and psychiatric [n = 183] adverse events [AEs]) endpoints were 
      analyzed separately using a binary logistic regression model. In IA patients 
      receiving voriconazole monotherapy, no positive associations between voriconazole 
      exposure and efficacy or safety were identified. In IA patients receiving 
      combination therapy, no positive associations between voriconazole or 
      anidulafungin exposures and efficacy were identified. The 6-week survival rate 
      tended to increase as anidulafungin treatment duration increased; this finding 
      should be considered with caution. Additionally, in IA patients receiving 
      combination therapy, a positive association between voriconazole and 
      anidulafungin exposures (area under the curve [AUC] and trough concentration 
      [C(min)]) and hepatic AEs was established; a weak positive association between 
      voriconazole exposure (AUC and C(min)) and psychiatric AEs was also established, 
      but no association between voriconazole exposure and visual AEs was identified. 
      Besides the drug exposures, no other covariates (i.e., CYP2C19 genotype status, 
      age, weight, body mass index, sex, race, or neutropenia status) were identified 
      as significant predictors of the efficacy and safety endpoints in IA patients. 
      This study was registered on ClinicalTrials.gov (NCT00531479).
CI  - Copyright (c) 2014, American Society for Microbiology. All Rights Reserved.
FAU - Liu, Ping
AU  - Liu P
AD  - Clinical Pharmacology, Global Established Pharma Business, Pfizer Inc., Groton, 
      Connecticut, USA ping.liu@pfizer.com.
FAU - Mould, Diane R
AU  - Mould DR
AD  - Projections Research Inc., Phoenixville, Pennsylvania, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00531479
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140609
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antifungal Agents)
RN  - 0 (Echinocandins)
RN  - 9HLM53094I (Anidulafungin)
RN  - JFU09I87TR (Voriconazole)
SB  - IM
CIN - Antimicrob Agents Chemother. 58:4718.
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anidulafungin
MH  - Antifungal Agents/blood/*pharmacokinetics/pharmacology
MH  - Area Under Curve
MH  - Aspergillosis/blood/*drug therapy/microbiology
MH  - Aspergillus/drug effects/physiology
MH  - Biological Availability
MH  - Chemical and Drug Induced Liver Injury/etiology/physiopathology
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Echinocandins/adverse effects/blood/*pharmacokinetics
MH  - Female
MH  - Half-Life
MH  - Hallucinations/etiology/physiopathology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Models, Statistical
MH  - Photophobia/etiology/physiopathology
MH  - Prospective Studies
MH  - Voriconazole/adverse effects/blood/*pharmacokinetics
PMC - PMC4126689
EDAT- 2014/06/11 06:00
MHDA- 2015/09/01 06:00
PMCR- 2015/02/01
CRDT- 2014/06/11 06:00
PHST- 2014/06/11 06:00 [entrez]
PHST- 2014/06/11 06:00 [pubmed]
PHST- 2015/09/01 06:00 [medline]
PHST- 2015/02/01 00:00 [pmc-release]
AID - AAC.02809-13 [pii]
AID - 02809-13 [pii]
AID - 10.1128/AAC.02809-13 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2014 Aug;58(8):4727-36. doi: 10.1128/AAC.02809-13. 
      Epub 2014 Jun 9.