Theophylline dosing and pharmacokinetics for renal protection in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia
PEDIATRIC RESEARCH
Authors: Frymoyer, Adam; Van Meurs, Krisa P.; Drover, David R.; Klawitter, Jelena; Christians, Uwe; Chock, Valerie Y.
Abstract
Background Theophylline, a non-selective adenosine receptor antagonist, improves renal perfusion in the setting of hypoxia-ischemia and may offer therapeutic benefit in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing hypothermia. We evaluated the pharmacokinetics and dose-exposure relationships of theophylline in this population to guide dosing strategies. Methods A population pharmacokinetic analysis was performed in 22 neonates with HIE undergoing hypothermia who were part of a prospective study or retrospective chart review. Aminophylline (intravenous salt form of theophylline) was given per institutional standard of care for low urine output and/or rising serum creatinine (5 mg/kg intravenous (i.v.) load then 1.8 mg/kg i.v. q6h). The ability of different dosing regimens to achieve target concentrations (4-10 mg/L) associated with clinical response was examined. Results Birth weight was a significant predictor of theophylline clearance and volume of distribution (p < 0.05). The median half-life was 39.5 h (range 27.2-50.4). An aminophylline loading dose of 7 mg/kg followed by 1.6 mg/kg q12h was predicted to achieve target concentrations in 84% of simulated neonates. Conclusions In neonates with HIE undergoing hypothermia, theophylline clearance was low with a 50% longer half-life compared to full-term normothermic neonates without HIE. Dosing strategies need to consider the unique pharmacokinetic needs of this population. Impact Theophylline is a potential renal-protective therapy in neonates with HIE undergoing therapeutic hypothermia; however, the pharmacokinetics and dose needs in this population are not known. Theophylline clearance was low in neonates with HIE undergoing therapeutic hypothermia with a 50% longer half-life compared to full-term normothermic neonates without HIE. As theophylline is advanced in clinical development, dosing strategies will need to consider the unique pharmacokinetic needs of neonates with HIE undergoing therapeutic hypothermia.
Early and Late Efficacy on Wound Healing of Silver Nanoparticle Gel in Males after Circumcision
JOURNAL OF CLINICAL MEDICINE
Authors: Balzarro, Matteo; Rubilotta, Emanuele; Trabacchin, Nicolo; Soldano, Antonio; Cerrato, Clara; Migliorini, Filippo; Mancini, Vito; Pastore, Antonio Luigi; Carbone, Antonio; Cormio, Luigi; Carrieri, Giuseppe; Antonelli, Alessandro
Abstract
We evaluate the early and late safety and efficacy of silver nanoparticle (AgNPs) in wound healing after circumcision. This multicenter prospective comparative non-randomized observational study compares wound dressing with AgNPs (group A) vs. gentamicin cream (group B). Follow-up included objective evaluation at 10 and 30 days by the Southampton Scoring System (SSS) and Stony Brook Scar Evaluation Scale (SBSES). We enrolled 392 males: 194 in group A, and 198 in group B. At 10 days follow-up, in group A, the SSS scale was grade 1 in 49.5% and grade 2 in the remaining; meanwhile, in group B, grade 1 was in 58%, grade 2 in 34.3%, and grade 4 in 7.6%. At 30 days follow-up, grade 1 healing was 97.4% and 98.4% in group A and B, respectively. At 10 days follow-up, the mean SBSES score was 3.58 and 3.69 in group A and B, respectively; while at 30 days follow-up, 4.81 and 4.76 in group A and B, respectively. Only in group B did 7.6% of males have antibiotic therapy due to pus discharge. No patients needed surgical wound revision. AgNPs led to a late but safer healing, they were non-inferior to the antibiotic cream wound dressing efficacy, and they avoided pus discharge and the need for oral antibiotics due to their polymer material.