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Purpose: Serum posaconazole (POS) concentrations >500-700 and >1250 ng/mL are associated with successful prophylaxis and treatment of invasive fungal infections (IFIs), respectively. We investigated factors potentially contributing to inadequate serum POS concentrations.
Methods: Retrospective review was performed of all NIAID patients ≥18 yrs who received POS at NIH (9/2006 – 3/2012) and had ≥1 available serum POS concentration. ANOVA, Wilcoxon, and Fisher’s exact tests were used to assess the following variables for their influence on POS concentrations: race, sex, underlying diagnosis, gastrointestinal (GI) disease (diarrhea, CGD [chronic granulomatous disease] colitis), and indication (treatment/prophylaxis). P<0.05 was accepted as statistically significant.
Results: A total of 283 serum POS concentrations were available from 73 pts (66% male). Median (range) age and body weight were 28 (18-74) yrs and 60 (39-106) kg. Frequent underlying conditions were CGD (56%), Hyper-IgE syndrome (18%), and bronchiectasis (12%). POS was prescribed for prophylaxis, and treatment in 55% and 45% of patients, respectively. Median values for POS serum concentration and dose-adjusted concentration were 896 (<50 – 2845) ng/mL and 1.11 (0 – 4.74) ng/mL/mg, respectively. Failure to attain a concentration of 500, 700, and 1250 ng/mL occurred in 18%, 33%, and 81% of patients, respectively. Patients with CGD and GI disease had significantly lower POS concentrations than those who did not (p = 0.002 and 0.03 respectively). In addition, age was positively correlated with dose-adjusted concentration (p<0.001) with an estimated 0.24 ng/mL/mg increase in POS concentration per 10 yr age increase. Indication, race, and sex did not influence POS concentrations.
Conclusion: Achieving target POS concentrations for treatment and prophylaxis of IFIs may be impeded by CGD-related GI disease and younger age. Therapeutic drug monitoring would be particularly useful to ensure adequate POS exposure in these patient subsets, and as a test for patient adherence.