Population Pharmacokinetics and Safety of Oral Posaconazole in Children With Leukemia

Posaconazole as a new triazole antifungal agent with broad spectrum coverage, was recommended for prophylaxis of invasive fungal disease in adults. Some studies have demonstrated the relationship between posaconazole plasma concentration and efficacy and few data have been published in children with leukemia.The purpose of this study is to describe the off-label use of posaconazole oral suspensions in children;to figure out the relationship between concentration and clinical outcomes/ adverse events;to identify factors that influence plasma concentration.

Inclusion criteria

• 1、Patients age 2-14 years with acute leukemia (AML, ALL) undergoing chemotherapy and neutropenia expected to last at least 7 days.

2、Karnofsky/Lansky score of 60% or greater. 3、defined as alanine transaminase (ALT) <3 x upper limit of normal (ULN),aspartate aminotransferase (AST) <3 x ULN; serum bilirubin and alkaline phosphatase <2 x ULN.

4、No other treatment and combination of triazoles antifungals and drugs like vincristine, sirolimus, cyclosporine etc.

5、Able to take oral medication or take medication via enteral feeding tube. 6、Ability to give informed consent. 7、No history of anaphylaxis attributed to the azole class of antifungal agents.

Exclusion criteria

• 1、Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or major organ dysfunction.

2、Subject is not considered eligible for this clinical research program with posaconazole.

3、Use of medications that are known to interact with posaconazole and that may lead to life-threatening side to effects.