PMID- 20001450
OWN - NLM
STAT- MEDLINE
DCOM- 20100430
LR  - 20131125
IS  - 1473-4877 (Electronic)
IS  - 0300-7995 (Linking)
VI  - 26
IP  - 2
DP  - 2010 Feb
TI  - Population pharmacokinetics of posaconazole in neutropenic patients receiving 
      chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome.
PG  - 397-405
LID - 10.1185/03007990903485056 [doi]
AB  - OBJECTIVE: The relationship between patient characteristics and posaconazole 
      exposures was evaluated in a population pharmacokinetic (PK) model using trial 
      data from neutropenic patients administered oral posaconazole suspension as 
      antifungal prophylaxis. METHODS: Data were analyzed using nonlinear mixed-effects 
      modeling. Covariates were tested using the forward addition, Objective Function 
      (OF) cut-off of 3.84, followed by the backward elimination (OF cut-off 10.88) 
      steps in NONMEM. These covariates included demographics, mucositis, neutropenia, 
      vomiting, diarrhea, proton pump inhibitor (PPI) or H(2)-receptor antagonist usage 
      and baseline bilirubin or baseline gamma-glutamyl transferase (GGT) levels > or 
      =2 x upper limit of normal (ULN). A correlation between posaconazole PK and the 
      occurrence of invasive fungal infection (IFI) was also examined. RESULTS: 
      Statistically significant associations were demonstrated between posaconazole PK 
      and diarrhea, PPI intake, race, and baseline GGT and bilirubin levels. These 
      covariates did not predominate in patients who developed IFI. CONCLUSION: This 
      analysis provides information regarding the correlation of patient covariates 
      with posaconazole exposures estimated in a clinical setting. The results of this 
      analysis agree with previously reported analyses. However, because of the 
      successful prophylaxis and the low number of posaconazole-treated patients with 
      IFI proven or probable (IFIPP), the absence of a statistically significant 
      relationship between IFIPP and exposure may not mean this relationship does not 
      exist. A meta-analysis of several efficacy trials or exploring alternate 
      composite endpoints for efficacy may be needed to answer this question.
FAU - AbuTarif, M A
AU  - AbuTarif MA
AD  - Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 
      07033, USA. mabutarif@gmail.com
FAU - Krishna, G
AU  - Krishna G
FAU - Statkevich, P
AU  - Statkevich P
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Med Res Opin
JT  - Current medical research and opinion
JID - 0351014
RN  - 0 (Antifungal Agents)
RN  - 0 (Triazoles)
RN  - 6TK1G07BHZ (posaconazole)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibiotic Prophylaxis/methods
MH  - Antifungal Agents/pharmacokinetics/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/*adverse effects/*therapeutic use
MH  - Female
MH  - Humans
MH  - Leukemia, Myeloid, Acute/*drug therapy/metabolism
MH  - Male
MH  - Middle Aged
MH  - Mycoses/etiology/*prevention & control
MH  - Myelodysplastic Syndromes/*drug therapy/metabolism
MH  - Neutropenia/*chemically induced/complications/metabolism
MH  - Population
MH  - Single-Blind Method
MH  - Triazoles/*pharmacokinetics/therapeutic use
MH  - Young Adult
EDAT- 2009/12/17 06:00
MHDA- 2010/05/01 06:00
CRDT- 2009/12/17 06:00
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/05/01 06:00 [medline]
AID - 10.1185/03007990903485056 [doi]
PST - ppublish
SO  - Curr Med Res Opin. 2010 Feb;26(2):397-405. doi: 10.1185/03007990903485056.