PMID- 25106074
OWN - NLM
STAT- MEDLINE
DCOM- 20150420
LR  - 20220316
IS  - 1872-7913 (Electronic)
IS  - 0924-8579 (Linking)
VI  - 44
IP  - 3
DP  - 2014 Sep
TI  - Voriconazole pharmacokinetics and exposure-response relationships: assessing the 
      links between exposure, efficacy and toxicity.
PG  - 183-93
LID - S0924-8579(14)00185-X [pii]
LID - 10.1016/j.ijantimicag.2014.05.019 [doi]
AB  - The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal 
      activity and is the first-line treatment for invasive aspergillosis. Highly 
      variable, non-linear pharmacokinetics, metabolism via the polymorphic 
      drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) 
      including hepatotoxicity and neurotoxicity complicate the clinical utility of 
      VCZ. As interest in optimising VCZ treatment has increased, a growing number of 
      studies have examined the relationships between VCZ exposure and efficacy in the 
      treatment and prevention of invasive fungal infections, as well as associations 
      with VCZ-related AEs. This review provides a critical analysis of VCZ 
      pharmacokinetics and exposure-response (E-R) relationships, assessing the links 
      between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been 
      associated with a higher incidence of treatment failure; fewer studies have 
      addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity 
      appears common at high VCZ concentrations and can be minimised by maintaining 
      concentrations below the recommended upper concentration thresholds; 
      hepatotoxicity appears to be associated with increased VCZ exposure but is also 
      prevalent at low concentrations. Further research should aim to inform and 
      optimise the narrow therapeutic range of VCZ as well as develop interventions to 
      individualise VCZ dosing to achieve maximal efficacy with minimal toxicity.
CI  - Copyright (c) 2014 Elsevier B.V. and the International Society of Chemotherapy. All 
      rights reserved.
FAU - Dolton, Michael J
AU  - Dolton MJ
AD  - Faculty of Pharmacy, The University of Sydney, Sydney, NSW, Australia.
FAU - McLachlan, Andrew J
AU  - McLachlan AJ
AD  - Faculty of Pharmacy, The University of Sydney, Sydney, NSW, Australia; Centre for 
      Education and Research on Ageing, Concord Repatriation General Hospital, Sydney, 
      NSW, Australia. Electronic address: andrew.mclachlan@sydney.edu.au.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20140707
PL  - Netherlands
TA  - Int J Antimicrob Agents
JT  - International journal of antimicrobial agents
JID - 9111860
RN  - 0 (Antifungal Agents)
RN  - JFU09I87TR (Voriconazole)
SB  - IM
MH  - Antifungal Agents/administration & dosage/adverse 
      effects/*pharmacokinetics/pharmacology
MH  - Aspergillosis/drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Drug-Related Side Effects and Adverse Reactions/pathology
MH  - Humans
MH  - Treatment Failure
MH  - Voriconazole/administration & dosage/adverse 
      effects/*pharmacokinetics/pharmacology
OTO - NOTNLM
OT  - Antifungal
OT  - Azoles
OT  - Exposure-response
OT  - Pharmacodynamics
OT  - Pharmacokinetics
OT  - Voriconazole
EDAT- 2014/08/12 06:00
MHDA- 2015/04/22 06:00
CRDT- 2014/08/10 06:00
PHST- 2014/05/17 00:00 [received]
PHST- 2014/05/19 00:00 [accepted]
PHST- 2014/08/10 06:00 [entrez]
PHST- 2014/08/12 06:00 [pubmed]
PHST- 2015/04/22 06:00 [medline]
AID - S0924-8579(14)00185-X [pii]
AID - 10.1016/j.ijantimicag.2014.05.019 [doi]
PST - ppublish
SO  - Int J Antimicrob Agents. 2014 Sep;44(3):183-93. doi: 
      10.1016/j.ijantimicag.2014.05.019. Epub 2014 Jul 7.