Patient participation in these processes was reported as sometimes limited, but parents and oncologists should continue to probe patients' abilities and desire to be involved in decision making. Future research should expand the DPM and explore how decisional priority and authority can be shared by oncologists with parents and even patients.
Posaconazole is a promising antifungal agent to be used prophylactically in hematologic patients aged 13 years or younger. Administering posaconazole oral suspension in a dosage of 120 mg/m tid results in adequate posaconazole plasma exposure, without significant adverse events.
Background: Posaconazole oral suspension emerged as a promising candidate for prophylaxis of invasive fungal infections in immunocompromised children. Its pharmacodynamic advantages include a broad spectrum of activity and a favorable safety profile. However, these are overshadowed by a large pharmacokinetic (PK) variability, potentially leading to subtherapeutic exposure. Methods: Data were obtained from a prospective interventional study, including hospitalized pediatric patients with a hematologic malignancy treated prophylactically with posaconazole oral suspension. A population PK model was built (NONMEM 7.4). The probability of target attainment (PTA; 100% T ≥0.7 mg/L) for prophylaxis under fixed, body weight-based, and body surface area-based dosing was evaluated using Monte Carlo simulation. Results: Fourteen patients contributed 112 posaconazole plasma concentrations. The PK of posaconazole was adequately described by a one-compartment model with lag time of 2.71 h [13%] (typical value [relative standard error]), nonlinear bioavailability ED50 99.1 mg/m 2 (prior knowledge), first-order absorption rate constant ka 0.325 h -1 [27%], apparent volume of distribution 1,150 L [34%], and apparent clearance 15.4 L/h [24%] (standardized to a 70-kg individual). The apparent bioavailability
Although physicians need to respect the wishes of children's legal representatives, they also have a duty to promote patients' best interests. We recommend that physicians employ a proactive stance in ensuring that children with cancer are appropriately informed about their diagnosis. In case of parents' arduous objections to full disclosure, an ethical consultation should be considered.
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