Pharmacokinetics and safety of tobramycin nebulization with the I-neb and PARI-LC Plus in children with cystic fibrosis: A randomized, crossover study.

AIMS: We aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I-neb device to the standard PARI-LC Plus nebulizer in children with cystic fibrosis. METHODS: A randomized, open-label, crossover study was performed. In 2 separate study visits, blood samples from 22 children were collected following TIS nebulization with I-neb (75 mg) and PARI-LC Plus (300 mg). Study visits were separated by 1 month, in which 1 of the study nebulizers was used twice daily. Tobramycin PK for both nebulizers was established using measured tobramycin concentrations and Bayesian PK modelling software. Hearing and renal function tests were performed to test for aminoglycoside associated toxicity. In addition to standard estimated glomerular filtration rate values, biomarkers for tubular injury (KIM-1 and NAG) were measured. Patient and nebulizer satisfaction were assessed. RESULTS: Inhalations were well tolerated and serum trough concentrations below the predefined toxic limit were reached with no significant differences in PK parameters between nebulizers. Results of audiometry and estimated glomerular filtration rate revealed no abnormalities. However, increased urinary NAG/creatinine ratios at visit 2 for both nebulizers suggest TIS-induced subclinical tubular kidney injury. Nebulization time was 50% shorter and patient satisfaction was significantly higher with the I-neb. CONCLUSIONS: Nebulization of 75 mg TIS with the I-neb in children with cystic fibrosis resulted in comparable systemic exposure to 300 mg TIS with the PARI-LC Plus and was well tolerated and preferred over the PARI-LC Plus. Long-term safety of TIS nebulization should be monitored clinically, especially regarding the effects on tubular kidney injury.

Intrapleural extravasation of epirubicin, 5-fluouracil, and cyclophosphamide, treated with dexrazoxane.

The extravasation of DNA-binding vesicant drugs, such as epirubicin, is a feared complication of chemotherapy and can lead to extensive damage at injury sites. We describe a 56-year-old woman with breast cancer who received adjuvant chemotherapy after a breast-preserving surgical procedure. Due to catheter tip misplacement, epirubicin, 5-fluouracil, and cyclophosphamide were administered intrapleurally. To minimize long-term sequelae, flushing of the cavities and systemic administration of steroids were performed. Besides this treatment, empirically, 3-day therapy with dexrazoxane was added to prevent tissue damage and the risk of cardiac damage. Because of the potential benefits of dexrazoxane and its relatively mild side effects, its use should be considered in cases of the intrapleural extravasation of anthracyclines. We do emphasis the need for stringent surgical and oncological nursing procedures when using central venous access catheters in oncology.