Micafungin (FK463) is a new parenteral echinocandin. A multicenter, phase I, open-label, sequential-group dose escalation study was conducted to assess the safety, tolerability, and pharmacokinetics of micafungin in neutropenic pediatric patients. A total of 77 patients stratified by age (2 to 12 and 13 to 17 years) received micafungin. Therapy was initiated at 0.5 mg/kg per day and escalated to higher dose levels of 1.0, 1.5, 2.0, 3.0, and 4.0 mg/kg per day. Micafungin was administered within 24 h of initiating broad-spectrum antibacterial antibiotics for the new onset of fever and neutropenia. The most common overall adverse events in the study population were diarrhea (19.5%), epistaxis (18.2%), abdominal pain (16.9%), and headache (16.9%). Nine patients (12%) experienced adverse events considered by the investigator to be possibly related to the study drug. The most common related events were diarrhea, vomiting, and headache, all occurring in two patients each. There was no evidence of a dose-limiting toxicity as defined within the prespecified criteria of this clinical protocol. There was one death during the study due to septic shock. The pharmacokinetic profiles for micafungin over the 0.5-to 4.0-mg/kg dose range demonstrated dose linearity. Clearance, volume of distribution, and half-life remained relatively constant over the dose range and did not change with repeated administration. The overall plasma pharmacokinetic profile was similar to that observed in adults. However, there was an inverse relation between age and clearance. For patients 2 to 8 years old, clearance was approximately 1.35 times that of patients >9 years of age. In summary, micafungin over a dosage range between 0.5 and 4.0 mg/kg/day in 77 febrile neutropenic pediatric patients displayed linear pharmacokinetics and increased clearance as a function of decreasing age.Advances in cytotoxic chemotherapy, transplantation procedures, and supportive care have increased survival in children with leukemia and other neoplasms (4,11,28). However, invasive fungal infections remain an important cause of infection-related mortality and morbidity in pediatric patients (1,6,9,14). Recent advances in the early diagnosis, prevention, and treatment of fungal infections offer hope to these patients (2, 10, 13). Among the newer classes of antifungal compounds are the echinocandins, which have offered broad-spectrum activity and a favorable safety profile in adult patients (3).Currently, the two most common invasive fungal infections in neutropenic adult and pediatric patients are caused by Candida spp. and Aspergillus spp. Micafungin (FK463; Fujisawa Healthcare, Inc., Deerfield, IL) is an intravenous antifungal compound of the echinocandin class. Micafungin acts by inhibiting the production of 1,3-␤-D-glucan, a key component in fungal cell wall synthesis (12). A semisynthetic lipopeptide, micafungin possesses in vitro and in vivo activity against a broad spectrum of Candida and Aspergillus species, including activity against azole-resistant Candida (8,1...

Programmable Intrathecal (IT) drug delivery systems are being increasingly used with radiation therapy for cancer treatment and palliation. Ionizing radiation is assumed to cause dysfunction of the programmable IT device. However, the dose limit and safety of the IT drug delivery device used concurrently with radiotherapy have not been extensively documented. Here we report a patient who underwent the implantation of an IT pump during radiotherapy. This device was subsequently directly exposed to radiation. Estimated cumulative doses to the pump were in the range of 1.28 to 9.98 Gy. The IT pump exposed to this high-dose radiation did not pose any risk to the patient or the environment. The device was queried during and after the completion of treatment and found to be functioning without fault. This is the first case description about the successful function of an IT drug delivery device directly exposed to ionizing radiation.