Subject(s)
Antiviral Agents/therapeutic use , Enzyme Inhibitors/therapeutic use , Influenza, Human/drug therapy , Oseltamivir/therapeutic use , Antiviral Agents/pharmacology , Enzyme Inhibitors/pharmacology , Humans , Influenza A virus , Influenza, Human/virology , Information Dissemination , Neuraminidase/antagonists & inhibitors , Oseltamivir/pharmacology , Treatment OutcomeABSTRACT
Infants are at increased risk for morbidity and mortality due to influenza. Until recently, few data were available with which to optimize oseltamivir dosing in this high-risk population. Here, data for 133 infants were pooled from two prospective pharmacokinetic/pharmacodynamic safety studies to develop a population pharmacokinetic model. A three-compartment model with allometric scaling of all clearance and volume parameters described the disposition of oseltamivir and its carboxylate metabolite (OC). Weight dependence, OC clearance, and volume of distribution increased linearly with age. Analyses showed no association between OC exposure and viral clearance, the development of resistance (phenotypic/genotypic), normalization of body temperature, or safety endpoints. Pharmacokinetic bridging showed that a 3 mg/kg dose yielded acceptable OC exposure and good tolerability while minimizing the risk of underexposure and resistance/treatment failure. These pharmacological analyses formed the basis of the US Food and Drug Administration's recent approval of oseltamivir treatment for infants with influenza aged as young as 2 weeks.
Subject(s)
Antiviral Agents/pharmacokinetics , Drug Dosage Calculations , Influenza, Human/drug therapy , Models, Biological , Oseltamivir/pharmacokinetics , Administration, Oral , Age Factors , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Antiviral Agents/blood , Biological Availability , Biotransformation , Body Weight , Carboxylic Acids/metabolism , Computer Simulation , Drug Resistance, Viral , Female , Humans , Infant , Infant, Newborn , Influenza, Human/blood , Influenza, Human/diagnosis , Influenza, Human/virology , Linear Models , Male , Oseltamivir/administration & dosage , Oseltamivir/adverse effects , Oseltamivir/bloodABSTRACT
The recent identification of fracturing of the retention wire in the Telectronics atrial lead, models 329-701 and 330-801, and the report of death due to cardiac tamponade caused by aortic puncture resulting from protrusion of the retention wire, necessitates fluoroscopic screening of these patients and the explantation of all leads identified to have the component failure. We present in this paper a percutaneous alternative to lead explantation in patients with protrusion of the retention wire through the polyurethane insulation and with an otherwise properly functioning atrial lead.